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Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome

  • M. E. Hirschtritt (a1), S. M. Darrow (a1), C. Illmann (a2), L. Osiecki (a2), M. Grados (a3), P. Sandor (a4), Y. Dion (a5), R. A. King (a6), D. Pauls (a2), C. L. Budman (a7), D. C. Cath (a8), E. Greenberg (a2), G. J. Lyon (a9), D. Yu (a2), L. M. McGrath (a10), W. M. McMahon (a11), P. C. Lee (a12), K. L. Delucchi (a1), J. M. Scharf (a2) (a13) (a14) and C. A. Mathews (a15)...
Abstract
Background

The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.

Method

OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.

Results

EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).

Conclusions

Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

Copyright
Corresponding author
*Address for correspondence: C. A. Mathews, M.D., Department of Psychiatry, University of Florida, 100 S. Newell Drive, L4-100, Gainesville, FL, 32610, USA. (E-mail: carolmathews@ufl.edu)
References
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Abramovitch, A, Dar, R, Mittelman, A, Schweiger, A (2013). Don't judge a book by its cover: ADHD-like symptoms in obsessive compulsive disorder. Journal of Obsessive-Compulsive and Related Disorders 2, 5361.
Abramovitch, A, Dar, R, Mittelman, A, Wilhelm, S (2015). Comorbidity between attention deficit/hyperactivity disorder and obsessive-compulsive disorder across the lifespan: a systematic and critical review. Harvard Review of Psychiatry 23, 245262.
Almasy, L, Blangero, J (1998). Multipoint quantitative-trait linkage analysis in general pedigrees. American Journal of Human Genetics 62, 11981211.
Alsobrook, JP II, Pauls, DL (2002). A factor analysis of tic symptoms in Gilles de la Tourette's syndrome. American Journal of Psychiatry 159, 291296.
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Publishing: Arlington, VA.
Arnsten, AF, Rubia, K (2012). Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders. Journal of the American Academy of Child and Adolescent Psychiatry 51, 356367.
Bloch, MH, Landeros-Weisenberger, A, Rosario, MC, Pittenger, C, Leckman, JF (2008). Meta-analysis of the symptom structure of obsessive-compulsive disorder. American Journal of Psychiatry 165, 15321542.
Cavanna, AE, Critchley, HD, Orth, M, Stern, JS, Young, MB, Robertson, MM (2011). Dissecting the Gilles de la Tourette spectrum: a factor analytic study on 639 patients. Journal of Neurology, Neurosurgery, and Psychiatry 82, 13201323.
Collett, BR, Crowley, SL, Gimpel, GA, Greenson, JN (2000). The factor structure of DSM-IV attention deficit-hyperactivity symptoms: a confirmatory factor analysis of the ADHD-SRS. Journal of Psychoeducational Assessment 18, 361373.
Darrow, SM, Hirschtritt, ME, Davis, LK, Illmann, C, Osiecki, L, Grados, M, Sandor, P, Dion, Y, King, R, Pauls, D, Budman, CL, Cath, DC, Greenberg, E, Lyon, GJ, Yu, D, McGrath, LM, McMahon, WM, Lee, PC, Delucchi, KL, Scharf, JM, Mathews, CA, Tourette Syndrome Association International Consortium for Genetics (2017). Identification of two heritable cross-disorder endophenotypes for Tourette syndrome. American Journal of Psychiatry 174, 387396.
Davis, LK, Yu, D, Keenan, CL, Gamazon, ER, Konkashbaev, AI, Derks, EM, Neale, BM, Yang, J, Lee, SH, Evans, P, Barr, CL, Bellodi, L, Benarroch, F, Berrio, GB, Bienvenu, OJ, Bloch, MH, Blom, RM, Bruun, RD, Budman, CL, Camarena, B, Campbell, D, Cappi, C, Cardona Silgado, JC, Cath, DC, Cavallini, MC, Chavira, DA, Chouinard, S, Conti, DV, Cook, EH, Coric, V, Cullen, BA, Deforce, D, Delorme, R, Dion, Y, Edlund, CK, Egberts, K, Falkai, P, Fernandez, TV, Gallagher, PJ, Garrido, H, Geller, D, Girard, SL, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Haddad, S, Heiman, GA, Hemmings, SM, Hounie, AG, Illmann, C, Jankovic, J, Jenike, MA, Kennedy, JL, King, RA, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Liu, C, Lochner, C, Lowe, TL, Macciardi, F, McCracken, JT, McGrath, LM, Mesa Restrepo, SC, Moessner, R, Morgan, J, Muller, H, Murphy, DL, Naarden, AL, Ochoa, WC, Ophoff, RA, Osiecki, L, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, SL, Renner, TJ, Reus, VI, Richter, MA, Riddle, MA, Robertson, MM, Romero, R, Rosario, MC, Rosenberg, D, Rouleau, GA, Ruhrmann, S, Ruiz-Linares, A, Sampaio, AS, Samuels, J, Sandor, P, Sheppard, B, Singer, HS, Smit, JH, Stein, DJ, Strengman, E, Tischfield, JA, Valencia Duarte, AV, Vallada, H, Van Nieuwerburgh, F, Veenstra-Vanderweele, J, Walitza, S, Wang, Y, Wendland, JR, Westenberg, HG, Shugart, YY, Miguel, EC, McMahon, W, Wagner, M, Nicolini, H, Posthuma, D, Hanna, GL, Heutink, P, Denys, D, Arnold, PD, Oostra, BA, Nestadt, G, Freimer, NB, Pauls, DL, Wray, NR, Stewart, SE, Mathews, CA, Knowles, JA, Cox, NJ, Scharf, JM (2013). Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genetics 9, e1003864.
Delucchi, KL, Katerberg, H, Stewart, SE, Denys, DA, Lochner, C, Stack, DE, den Boer, JA, van Balkom, AJ, Jenike, MA, Stein, DJ, Cath, DC, Mathews, CA (2011). Latent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder. Comprehensive Psychiatry 52, 334341.
Dumenci, L, McConaughy, SH, Achenbach, TM (2004). A hierarchical three-factor model of inattention-hyperactivity-impulsivity derived from the Attention Problems syndrome of the Teacher's Report Form. School Psychology Review 33, 287301.
Eapen, V, Fox-Hiley, P, Banerjee, S, Robertson, M (2004). Clinical features and associated psychopathology in a Tourette syndrome cohort. Acta Neurologica Scandinavica 109, 255260.
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1995). Structured Clinical Interview for DSM-IV Axis I Disorders-Non-Patient Edition (SCID-I/NP, version 2.0) . Biometrics Research Department, New York State Psychiatric Institute: New York.
Floyd, FJ, Widaman, KF (1995). Factor analysis in the development and refinement of clinical assessment instruments. Psychological Assessment 7, 286299.
Freitag, CM, Rohde, LA, Lempp, T, Romanos, M (2010). Phenotypic and measurement influences on heritability estimates in childhood ADHD. European Child & Adolescent Psychiatry 19, 311323.
Friedman-Hill, SR, Wagman, MR, Gex, SE, Pine, DS, Leibenluft, E, Ungerleider, LG (2010). What does distractibility in ADHD reveal about mechanisms for top-down attentional control? Cognition 115, 93103.
Frost, RO, Steketee, G, Tolin, DF (2011). Comorbidity in hoarding disorder. Depression and Anxiety 28, 876884.
Fullana, MA, Vilagut, G, Mataix-Cols, D, Adroher, ND, Bruffaerts, R, Bunting, B, de Almeida, JM, Florescu, S, de Girolamo, G, de Graaf, R, Haro, JM, Kovess, V, Alonso, J (2013). Is ADHD in childhood associated with lifetime hoarding symptoms? An epidemiological study. Depression and Anxiety 30, 741748.
Fyer, A, Endicott, J, Mannuzza, S, Klein, DF (1985). Schedule for Affective Disorders and Schizophrenia-Lifetime Version, Modified for the Study of Anxiety Disorders (SADS-LA) . Anxiety Disorders Clinic, New York State Psychiatric Institute: New York.
Grados, MA, Mathews, CA (2009). Clinical phenomenology and phenotype variability in Tourette syndrome. Journal of Psychosomatic Research 67, 491496.
Hirschtritt, ME, Darrow, SM, Illmann, C, Osiecki, L, Grados, M, Sandor, P, Dion, Y, King, RA, Pauls, DL, Budman, CL, Cath, DC, Greenberg, E, Lyon, GJ, Yu, D, McGrath, LM, McMahon, WM, Lee, PC, Delucchi, KL, Scharf, JM, Mathews, CA, Tourette Syndrome Association International Consortium for Genetics (TSAICG) (2016). Social disinhibition is a heritable subphenotype of tics in Tourette syndrome. Neurology 87, 497504.
Hirschtritt, ME, Lee, PC, Pauls, DL, Dion, Y, Grados, MA, Illmann, C, King, RA, Sandor, P, McMahon, WM, Lyon, GJ, Cath, DC, Kurlan, R, Robertson, MM, Osiecki, L, Scharf, JM, Mathews, CA, Tourette Syndrome Association International Consortium for Genetics (2015). Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome. JAMA Psychiatry 72, 325333.
Huisman-van Dijk, HM, Schoot, R, Rijkeboer, MM, Mathews, CA, Cath, DC (2016). The relationship between tics, OC, ADHD and autism symptoms: a cross-disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members. Psychiatry Research 237, 138146.
Katerberg, H, Delucchi, KL, Stewart, SE, Lochner, C, Denys, DA, Stack, DE, Andresen, JM, Grant, JE, Kim, SW, Williams, KA, den Boer, JA, van Balkom, AJ, Smit, JH, van Oppen, P, Polman, A, Jenike, MA, Stein, DJ, Mathews, CA, Cath, DC (2010). Symptom dimensions in OCD: item-level factor analysis and heritability estimates. Behavior Genetics 40, 505517.
Kaufman, J, Birmaher, B, Brent, D, Rao, U, Flynn, C, Moreci, P, Williamson, D, Ryan, N (1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry 36, 980988.
Leckman, JF, Denys, D, Simpson, HB, Mataix-Cols, D, Hollander, E, Saxena, S, Miguel, EC, Rauch, SL, Goodman, WK, Phillips, KA, Stein, DJ (2010). Obsessive-compulsive disorder: a review of the diagnostic criteria and possible subtypes and dimensional specifiers for DSM-V. Depression and Anxiety 27, 507527.
Leckman, JF, Sholomskas, D, Thompson, WD, Belanger, A, Weissman, MM (1982). Best estimate of lifetime psychiatric diagnosis: a methodological study. Archives of General Psychiatry 39, 879883.
Lo, Y, Mendell, NR, Rubin, DB (2001). Testing the number of components in a normal mixture. Biometrika 88, 767778.
Loehlin, JC (2004). Goodness of Fit Indices: Latent Variable Models. Lawrence Erlbaum Associates: Mahwah, NJ.
Lopez-Sola, C, Fontenelle, LF, Verhulst, B, Neale, MC, Menchon, JM, Alonso, P, Harrison, BJ (2016). Distinct etiological influences on obsessive-compulsive symptom dimensions: a multivariate twin study. Depression and Anxiety 33, 179191.
Mathews, CA, Grados, MA (2011). Familiality of Tourette syndrome, obsessive-compulsive disorder, and attention-deficit/hyperactivity disorder: heritability analysis in a large sib-pair sample. Journal of the American Academy of Child and Adolescent Psychiatry 50, 4654.
McGrath, LM, Yu, D, Marshall, C, Davis, LK, Thiruvahindrapuram, B, Li, B, Cappi, C, Gerber, G, Wolf, A, Schroeder, FA, Osiecki, L, O'Dushlaine, C, Kirby, A, Illmann, C, Haddad, S, Gallagher, P, Fagerness, JA, Barr, CL, Bellodi, L, Benarroch, F, Bienvenu, OJ, Black, DW, Bloch, MH, Bruun, RD, Budman, CL, Camarena, B, Cath, DC, Cavallini, MC, Chouinard, S, Coric, V, Cullen, B, Delorme, R, Denys, D, Derks, EM, Dion, Y, Rosario, MC, Eapen, V, Evans, P, Falkai, P, Fernandez, TV, Garrido, H, Geller, D, Grabe, HJ, Grados, MA, Greenberg, BD, Gross-Tsur, V, Grunblatt, E, Heiman, GA, Hemmings, SM, Herrera, LD, Hounie, AG, Jankovic, J, Kennedy, JL, King, RA, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, JF, Lennertz, L, Lochner, C, Lowe, TL, Lyon, GJ, Macciardi, F, Maier, W, McCracken, JT, McMahon, W, Murphy, DL, Naarden, AL, Neale, BM, Nurmi, E, Pakstis, AJ, Pato, MT, Pato, CN, Piacentini, J, Pittenger, C, Pollak, Y, Reus, VI, Richter, MA, Riddle, M, Robertson, MM, Rosenberg, D, Rouleau, GA, Ruhrmann, S, Sampaio, AS, Samuels, J, Sandor, P, Sheppard, B, Singer, HS, Smit, JH, Stein, DJ, Tischfield, JA, Vallada, H, Veenstra-VanderWeele, J, Walitza, S, Wang, Y, Wendland, JR, Shugart, YY, Miguel, EC, Nicolini, H, Oostra, BA, Moessner, R, Wagner, M, Ruiz-Linares, A, Heutink, P, Nestadt, G, Freimer, N, Petryshen, T, Posthuma, D, Jenike, MA, Cox, NJ, Hanna, GL, Brentani, H, Scherer, SW, Arnold, PD, Stewart, SE, Mathews, CA, Knowles, JA, Cook, EH, Pauls, DL, Wang, K, Scharf, JM (2014). Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study. Journal of the American Academy of Child and Adolescent Psychiatry 53, 910919.
Muthén, B, du Toit, SHC, Spisic, D (1997). Robust inference using weighted least squares and quadratic estimating equations in latent variable modeling with categorical and continuous outcomes. Psychometrika 75, 145.
Muthén, LK, Muthén, BO (1998–2012). Mplus User's Guide, 7th edn. Muthén & Muthén: Los Angeles, CA.
Pauls, DL, Leckman, JF, Cohen, DJ (1993). Familial relationship between Gilles de la Tourette's syndrome, attention deficit disorder, learning disabilities, speech disorders, and stuttering. Journal of the American Academy of Child and Adolescent Psychiatry 32, 10441050.
Pillow, DR, Pelham, WE Jr, Hoza, B, Molina, BS, Stultz, CH (1998). Confirmatory factor analyses examining attention deficit hyperactivity disorder symptoms and other childhood disruptive behaviors. Journal of Abnormal Child Psychology 26, 293309.
Polanczyk, GV, Eizirik, M, Aranovich, V, Denardin, D, da Silva, TL, da Conceicao, TV, Pianca, TG, Rohde, LA (2003). Interrater agreement for the schedule for affective disorders and schizophrenia epidemiological version for school-age children (K-SADS-E). Revista brasileira de psiquiatria (Sao Paulo, Brazil: 1999) 25, 8790.
Preacher, KJ, Zhang, G, Kim, C, Mels, G (2013). Choosing the optimal number of factors in exploratory factor analysis: a model selection perspective. Multivariate Behavioral Research 48, 2856.
Raykov, T, Marcoulides, GA (2006). Parameter and Model Identification: A First Course in Structural Equation Modeling. Lawrence Erlbaum Associates: Mahwah, NJ.
Robertson, MM, Althoff, RR, Hafez, A, Pauls, DL (2008). Principal components analysis of a large cohort with Tourette syndrome. British Journal of Psychiatry: The Journal of Mental Science 193, 3136.
Schwarz, G (1978). Estimating the dimension of a model. Annals of Statistics 6, 461464.
Storch, EA, Murphy, TK, Geffken, GR, Soto, O, Sajid, M, Allen, P, Roberti, JW, Killiany, EM, Goodman, WK (2004). Further psychometric properties of the Tourette's Disorder Scale-Parent Rated version (TODS-PR). Child Psychiatry and Human Development 35, 107120.
Tolin, DF, Villavicencio, A, Umbach, A, Kurtz, MM (2011). Neuropsychological functioning in hoarding disorder. Psychiatry Research 189, 413418.
Toplak, ME, Pitch, A, Flora, DB, Iwenofu, L, Ghelani, K, Jain, U, Tannock, R (2009). The unity and diversity of inattention and hyperactivity/impulsivity in ADHD: evidence for a general factor with separable dimensions. Journal of Abnormal Child Psychology 37, 11371150.
Tourette Syndrome Association International Consortium for Genetics (1999). A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. American Journal of Human Genetics 65, 14281436.
Tourette Syndrome Association International Consortium for Genetics (2007). Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. American Journal of Human Genetics 80, 265272.
Wang, Z, Maia, TV, Marsh, R, Colibazzi, T, Gerber, A, Peterson, BS (2011). The neural circuits that generate tics in Tourette's syndrome. American Journal of Psychiatry 168, 13261337.
Zhang, T, Wang, J, Yang, Y, Wu, Q, Li, B, Chen, L, Yue, Q, Tang, H, Yan, C, Lui, S, Huang, X, Chan, RC, Zang, Y, He, Y, Gong, Q (2011). Abnormal small-world architecture of top-down control networks in obsessive-compulsive disorder. Journal of Psychiatry & Neuroscience: JPN 36, 2331.
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