Background
Although susceptibility loci exist for Gilles de la Tourette syndrome (GTS), no causative
gene has been identified, perhaps in part because of phenotypic heterogeneity. This
study used latent class analyses (LCA) to identify GTS subphenotypes and assess characteristics
and heritability of the classes.
Methods
The study included 952 individuals from 222 GTS families recruited for genetic studies.
LCA identified a best-fit model for combinations of the diagnoses of GTS, obsessive-compulsive
disorder (OCD), OC symptoms and behaviors (OCS/OCB), and attention-deficit/hyperactivity
disorder (ADHD) in a random sample of one sibling from each family (n = 197), a replication sample randomly chosen from the remaining siblings (n = 203), and in the entire sample (all siblings and parents, N = 952). Heritabilities were assessed for all categoric diagnoses and LCA classes
using a variance components approach.
Results
In this large sample of GTS sib pairs and their parents, three GTS-affected groups
were identified—GTS + OCS/OCB (Class III), GTS + OCD (Class IV), and GTS + OCD + ADHD
(Class V)—in addition to a minimally affected class (I) and a small chronic tics +
OCD class (II). A preponderance of males and younger age at onset was found in more
comorbidly affected classes. Only the GTS + OCD + ADHD class was highly heritable.
Conclusions
Our data suggest that GTS classes may represent distinct entities, with both shared
and unique etiologies. In particular, GTS + OCD + ADHD may represent a separate, heritable
phenotype that can be used to further inform genetic studies.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnostic and Statistical Manual of Mental Disorders—IV.Author, Washington, DC1994
- The behavioral spectrum of tic disorders: A community-based study.Neurology. 2002; 59: 414-420
- Hypothesis III.Arch Neurol. 1997; 54: 475-483
- The inheritance of Gilles de la Tourette's syndrome and associated behaviors.N Engl J Med. 1986; 315: 993-997
- Segregation and linkage analyses of Tourette's syndrome and related disorders.J Am Acad Child Adolesc Psychiatry. 1990; 29: 195-203
- The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: The Hopkins OCD family study.Biol Psychiatry. 2001; 50: 559-565
- Gilles de la Tourette's syndrome and obsessive-compulsive disorder.Arch Gen Psychiatry. 1986; 43: 1180-1182
- Familial relationship between Gilles de la Tourette's syndrome, attention deficit disorder, learning disabilities, speech disorders, and stuttering.J Am Acad Child Adolesc Psychiatry. 1993; 32: 1044-1050
- Children at familial risk for Tourette's disorder: Child and parent diagnoses.Am J Med Genet B Neuropsychiatr Genet. 2003; 121: 105-111
- A controlled family study of attention-deficit/hyperactivity disorder and Tourette's disorder.J Am Acad Child Adolesc Psychiatry. 2006; 45: 1354-1362
- Evidence for autosomal dominant transmission in Tourette's syndrome.Br J Psychiatry. 1993; 162: 593-596
- Intermediate inheritance of Tourette syndrome, assuming assortative mating.Am J Hum Genet. 1995; 57: 682-689
- Complex segregation analysis of families ascertained through Gilles de la Tourette syndrome.Genet Epidemiol. 2000; 18: 33-47
- Family study and segregation analysis of Tourette syndrome: Evidence for a mixed model of inheritance.Am J Hum Genet. 1996; 59: 684-693
- Further evidence for linkage of Gilles de la Tourette syndrome (GTS) susceptibility loci on chromosomes 2p11, 8q22 and 11q23–24 in South African Afrikaners.Am J Med Genet. 2001; 105: 163-167
- Sequence variants in SLITRK1 are associated with Tourette's syndrome.Science. 2005; 310: 317-320
- Significant linkage for Tourette syndrome in a large French Canadian family.Am J Hum Genet. 2000; 67: 1008-1013
- A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome.Am J Hum Genet. 1999; 65: 1428-1436
- Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families.Am J Hum Genet. 2007; 80: 265-272
- Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.J Am Acad Child Adolesc Psychiatry. 1997; 36: 980-988
- The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale of tic severity.J Am Acad Child Adolesc Psychiatry. 1989; 28: 566-573
- Web-based consensus diagnosis for genetics studies of Gilles de la Tourette syndrome.Adv Neurol. 2006; 99: 136-143
- MPLUS: Statistical Analyses with Latent Variables.3rd ed. Muthen and Muthen, Los Angeles, CA2004
- A new look at the statistical model identification.IEEE Trans Automatic Control. 1974; 19: 716-723
- Estimating the dimension of a model.Ann Stat. 1978; 6: 461-464
- Multipoint quantitative-trait linkage analysis in general pedigrees.Am J Hum Genet. 1998; 62: 1198-1211
- Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder.Psychiatr Clin North Am. 2000; 23: 563-586
- An integrative theory of attention-deficit/ hyperactivity disorder based on the cognitive and affective neurosciences.Dev Psychopathol. 2005; 17: 785-806
- Executive function, memory, and learning in Tourette's syndrome.Neuropsychology. 2003; 17: 247-254
- Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders.Arch Gen Psychiatry. 2000; 57: 364-372
- Increased number of subcortical hyperintensities on MRI in children and adolescents with Tourette's syndrome, obsessive-compulsive disorder, and attention deficit hyperactivity disorder.Am J Psychiatry. 2006; 163: 1106-1108
- Validity of the behavior rating inventory of executive function in children with ADHD and/or Tourette syndrome.Arch Clin Neuropsychol. 2002; 17: 643-662
- Attention deficit hyperactivity disorder: The childhood co-morbidity that most influences the disability burden in Tourette syndrome.Adv Neurol. 2006; 99: 17-21
- Disentangling the effects of Tourette syndrome and attention deficit hyperactivity disorder on cognitive and behavioral phenotypes.Brain Dev. 2007; 29: 413-420
- The structure of obsessionality among young adults.Depress Anxiety. 2004; 20: 77-85
- Tic or compulsion?.Behav Modif. 2005; 29: 784-799
- Obsessive compulsive symptoms in Gilles de la Tourette syndrome and obsessive compulsive disorder: Differences by diagnosis and family history.Am J Med Genet. 1997; 74: 432-438
- Obsessive-compulsive disorder in Tourette syndrome.Adv Neurol. 2006; 99: 22-38
- Psychopathology in children and adolescents with Tourette's syndrome: A controlled study.Brain Dev. 2006; 28: 69-75
- Tourette's disorder with and without obsessive-compulsive disorder in adults: Are they different?.J Nerv Ment Dis. 1998; 186: 201-206
- Sensory phenomena in obsessive-compulsive disorder and Tourette's disorder.J Clin Psychiatry. 2000; 61: 150-156
- Candidate locus for Gilles de la Tourette syndrome/obsessive compulsive disorder/chronic tic disorder at 18q22.Am J Med Genet A. 2004; 130: 37-39
- A factor analysis of tic symptoms in Gilles de la Tourette's syndrome.Am J Psychiatry. 2002; 159: 291-296
- Tic symptom profiles in subjects with tourette syndrome from two genetically isolated populations.Biol Psychiatry. 2006;
- The Gilles de la Tourette syndrome: A principal component factor analytic study of a large pedigree.Psychiatr Genet. 2007; 17: 143-152
- [Genetic linkage analysis of Gilles de la Tourette Syndrome in a Colombian family.].Rev Neurol. 2006; 42: 211-216
Article info
Publication history
Published online: March 25, 2008
Accepted:
January 3,
2008
Received in revised form:
December 13,
2007
Received:
July 24,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
