Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome

doi:10.1016/S0022-3956(97)00028-9

Journal of Psychiatric Research

Volume 31, Issue 5, September–October 1997, Pages 519-530

https://doi.org/10.1016/S0022-3956(97)00028-9 Get rights and content

Abstract

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurence of tic disorders and OCS might indicate heterogeneity of TS.

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Cingulate role in Tourette syndrome
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Citation Excerpt :
Although dopaminergic pathways (Maia and Conceição, 2018) within cortico-striato-pallido-thalamo-cortical circuits (here abbreviated “CSTC” circuits) are most suspect, involvement of glutamatergic, GABAergic, noradrenergic, and histaminergic neurotransmission has also been proposed (Leckman et al., 2010; Yael et al., 2015). Family studies of TS consistently show an increase of 10–100-fold in tics and TS in first-degree relatives of TS patients relative to control families, indicating a strong genetic component (Pauls et al., 1991; Hebebrand et al., 1997; Stewart et al., 2006). Recent work suggests that TS is a genetically heterogeneous condition, with multiple vulnerability loci scattered across the genome (Pauls et al., 2014a).
This chapter comprehensively reviews the published record for neurosurgical, neurostimulatory, and neuroimaging evidence of the involvement of the cingulate gyrus in Gilles de la Tourette syndrome (TS). The most noteworthy evidence comes from neuroimaging. Neuroimaging findings were rarely exclusive to the cingulate cortex and tended to implicate multiple other cortices as well. Some results are reflective of obsessive–compulsive (OC) symptoms of TS. Copious findings, however, drawn from structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), resting-state functional magnetic resonance imaging (rsfMRI), task fMRI, and positron emission tomography (PET) implicate six of the eight cingulate subregions in TS. Gauged by MRI, cortical thinning and/or below-normal volume are seen in subgenual anterior cingulate cortex (sACC), pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and posterior middle cingulate cortex (pMCC), correlating with tic severity in sACC, pACC, and aMCC. Moreover, in pMCC, dorsal posterior cingulate cortex (dPCC), and ventral posterior cingulate cortex (vPCC), cortical thickness is a candidate biomarker shared across siblings with TS. Loss of cortex may reflect excitotoxicity secondary to insufficient local GABAergic inhibition, a notion supported by the few relevant MRS and PET studies conducted to date, recommending continued development of GABAergic and glutamatergic pharmacologic agents to treat TS. Measurements of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) obtained with DTI indicate that the white matter proximal to sACC, pACC, pMCC, and dPCC may also represent a seat of pathology in TS. rsfMRI reveals abnormal functional connectivity of pACC and dPCC with the globus pallidus internus, a favored target of therapeutic deep brain stimulation (DBS) for TS. In whole-brain network (graph theory) analysis, dPCC functional connectivity is related to the severity and complexity of tics. In task fMRI, in contrast, the pMCC seems to play a preeminent role in premonitory urges and preparation for tics as well as normal urges to urinate, swallow, and yawn. Strong monkey PET and EEG evidence ties vocal tics to spike discharges, α-activity, and regional blood flow in the pACC unleashed by failure of GABAergic inhibition in the ventral striatum. Tic suppression in fMRI scans is associated with increased blood oxygenation level-dependent activity in sACC, pACC, and aMCC, but decreased activity in pMCC and dPCC. Activity in the former three subregions may represent volitional effort, physical discomfort, and emotional distress that accompanies mounting tic urges; pMCC and dPCC may be more instrumental in amplifying than suppressing urges. Needs for future neuroimaging work in TS include longitudinal studies—particularly those striving to predict which individual pediatric patients will continue to suffer from TS as adults and studies of treatment response—particularly of behavioral therapies, which are as efficacious as pharmacology. Transcranial magnetic stimulation and related therapies such as cranial electrotherapy stimulation, which showed good efficacy in a recent trial, merit continued exploration. TS research using DTI, MRS, and PET will no doubt continue to benefit in coming years from technological advances such as ultrahigh-field scanners, multichannel head coils, and novel (including GABAergic and glutamatergic) ligands.
The familiality of specific symptoms of obsessive-compulsive disorder
2016, Psychiatry Research
Citation Excerpt :
The results regarding symmetry/ordering symptoms were rather surprising. Studies (Hebebrand et al., 1997; Leckman et al., 2003; 2010) so far have indicated that symmetry/ordering symptoms and “just right experiences” are associated with higher rates of OCD in first-degree relatives, an earlier age of onset of OCD and comorbid tics. In this study, there was a later mean age of onset of OCD in patients reporting a family history of symmetry/ordering symptoms.
This study aimed to assess whether a family history of specific OCD symptoms was associated with the same OCD symptoms in study participants. Participants were sampled from the Nepean OCD study (N=206) and were assessed with the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC) and the Vancouver Obsessional Compulsive Inventory (VOCI) in order to determine their OCD symptoms. A family history screen was used to determine whether participants had a first-degree relative with a history of any of the following specific symptoms: hoarding, contamination/cleaning, symmetry/ordering, doubt/checking and/or other OCD symptoms. The characteristics of participants with a family history of a specific OCD symptom were compared to those of participants with a family history of any other OCD symptom. This was repeated for each specific OCD symptom. The roles of co-occurring tics and age of onset of OCD were also assessed. Distinct familial associations were detected for the symptoms of hoarding and contamination/cleaning. Age of onset of OCD was significantly younger in participants who reported a family history of “other” symptoms. These findings suggest that certain OCD symptom dimensions are more familial than others, which has significant implications for aetiology of OCD.
The relationship between tics, OC, ADHD and autism symptoms: A cross- disorder symptom analysis in Gilles de la Tourette syndrome patients and family-members
2016, Psychiatry Research
Gilles de la Tourette's syndrome (GTS) is a disorder in which obsessive-compulsive (OC), Attention Deficit Hyperactivity Disorder (ADHD) and autism symptoms occur in up to 60% of patients, suggesting shared etiology. We explored the phenotypic structure of tic, OC, ADHD, and autism symptoms as measured by the YGTSS,Y-BOCS,CAARS and AQ, in 225 GTS patients and 371 family members. First, Confirmatory Factor Analyses (CFA) were performed on the symptom structure of each separate symptom scale. Second, the symptom dimensions derived from each scale were combined in one model, and correlations between them were calculated. Using the correlation matrix, Exploratory Factor Analyses (EFA) were performed on the symptom dimensions across the scales. EFA revealed a five factor structure: tic/aggression/symmetry; OC symptoms/compulsive tics/ numbers and patterns; ADHD symptoms; autism symptoms; and hoarding/inattention symptoms. The results are partly in line with the traditional categorical boundaries of the symptom scales used, and partly reveal a symptom structure that cuts through the diagnostic categories. This phenotypic structure might more closely reflect underlying etiologies than a structure that classically describes GTS patients according to absence or presence of comorbid OCD, ADHD and autism, and might inform both future genetic and treatment studies.
Genetics of Tourette Syndrome
2015, Movement Disorders: Genetics and Models: Second Edition
The concept that Tourette syndrome (TS) has a “hereditary” etiology can be traced back to Armand Trousseau's monograph, published in 1873, 12 years before Georges Gilles de la Tourette's celebrated publication. In his monograph describing patients with nonpainful tics, Trousseau noted that family members also exhibited tics and suggested the disorder was hereditary. Gilles de la Tourette, in his classic paper, included Trousseau's patients as examples and also noted family members of his own patients were affected with tics. Historically, these anecdotal examples led to conducting a series of genetic epidemiologic studies to answer specific questions into the inheritance of the presence of tics as a trait. Is the trait familial? What proportion of familiarity is genetic? Where is/are the gene(s) located? This chapter will summarize the historical evidence, review the current understanding of genetic architecture, and suggest future prospects for understanding the genetics of TS.
Trio study and meta-analysis support the association of genetic variation at the serotonin transporter with early-onset obsessive-compulsive disorder
2014, Neuroscience Letters
Despite compelling evidence for major genetic contributions to the etiology of obsessive–compulsive disorder (OCD), few genetic variants have been consistently associated with this debilitating illness. Molecular genetic studies in children and adolescents with OCD are of particular interest, since early onset of the disease has been observed to be associated with increased familiality. We replicate here for the first time in early-onset OCD patients, a previously reported association of OCD with the common gain-of-function L_A allele at the serotonin transporter linked polymorphic region known as 5-HTTLPR in a collection of parent-offspring trios. The present meta-analysis of this recently refined serotonin transporter gene variant revealed further support for the L_A allele conferring increased genetic susceptibility to OCD. We conclude that the 5-HTTLPR is currently the single best supported risk variant for OCD, in regards of early-onset OCD, albeit of modest effect size and the possibility that the conferred risk might not be specific to OCD.
The genetic basis of Gilles de la Tourette Syndrome
2013, Neuroscience and Biobehavioral Reviews
Gilles de la Tourette Syndrome (TS) is a neuropsychiatric disorder that is caused by a likely complex genetic basis, interacting with environmental factors. Just as multiple large scale collaborative projects for TS are starting out and the first ever genomewide association study for TS has been published, this review provides a synthetic overview of more than two decades of active research. Studies of the dopaminergic and serotonergic pathways, have yielded inconsistent results, although, for instance, the involvement of DRD2, MAO-A, and DAT1 has been supported by independent findings. The study of chromosomal aberrations in TS etiology has implicated multiple genes, with SLITRK1 being the most prominent example. Common underlying themes with other neurodevelopmental disorders are emerging and attention on neurexins, neuroligins, and genes from the histaminergic and glutamatergic pathways is increased. Propelled by the gradual availability of large scale TS cohorts, and novel methodologies for the study of both common and rare genetic variants, the new era of TS genetics holds the promise to identify novel targets for improved therapies.

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Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome

Abstract

Psychiatric Research

Journal of the American Academy of Child and Adolescent Psychiatry

Comprehensive Psychiatry

The Lancet

Biological Psychiatry

Journal of the American Academy of Child and Adolescent Psychiatry

Journal of the American Academy of Child and Adolescent Psychiatry

Comprehensive Psychiatry

Genetic analysis of Tourette syndrome suggesting major gene effect

American Journal of Psychiatry

A family study of obsessive-compulsive disorder

Archives of General Psychiatry

The natural history of Tourette's syndrome

Mental play in Gilles de la Tourette's syndrome and obsessive-compusive disorder

British Journal of Psychiatry

Descriptive and diagnostic classification of tic disorders

Detection of major gene for Gilles de la Tourette syndrome

American Journal of Human Genetics