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Principal Components Analysis of a Large Cohort with Tourette Syndrome Mary M

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Principal Components Analysis of a Large Cohort with Tourette Syndrome Mary M The British Journal of Psychiatry (2008) 193, 31–36. doi: 10.1192/bjp.bp.107.039909 Principal components analysis of a large cohort with Tourette syndrome Mary M. Robertson, Robert R. Althoff, Adam Hafez and David L. Pauls Background Tourette syndrome is a heterogeneous familial disorder for complex motor tics; (3) simple tics; (4) compulsive which the genetic mechanisms are unknown. A better behaviours; and (5) touching self. Individuals with co- characterisation of the phenotype may help identify occurring attention-deficit hyperactivity disorder had susceptibility genes. significantly higher factor scores on Factors 1 and 3, whereas individuals with co-occurring obsessive–compulsive Aims disorder and behaviours had significantly higher factor scores To extend previous factor-analytic studies of the for Factors 1–4. syndrome. Method Conclusions Symptom data from 410 people with Tourette syndrome These findings add to the growing body of evidence that were included in agglomerative hierarchical cluster and Tourette syndrome is not a unitary condition and can be principal components analyses. disaggregated into more homogeneous symptom components. Results Five factors were observed, characterised by: (1) socially Declaration of interest inappropriate behaviours and other complex vocal tics; (2) None. Funding detailed in Acknowledgements. Tourette syndrome (Tourette disorder, DSM–IV–TR) is charac- Alsobrook & Pauls23 conducted a principal components factor terised by the presence of multiple motor and one or more analysis on a cohort of 85 individuals with Tourette syndrome vocal/phonic tics present for more than a year.1,2 Tics wax and and reported four factors: Factor 1 (APF1) was characterised by wane over time and do not necessarily occur concurrently. The behaviours that included coprolalia, ‘aggressive’ and self-injurious diagnosis of Tourette syndrome is relatively straightforward, but behaviours; Factor 2 (APF2) was characterised by simple and there is considerable clinical variability across individuals. The complex motor tics and simple vocal/phonic tics (e.g. noises, importance of evaluating the individual elements of a complex but no actual words); Factor 3 (APF3) was characterised by disorder such as Tourette syndrome cannot be overstated in terms ‘compulsive-like’ behaviours such as forced touching, repetitive of research into the underpinnings of the disorder and its clinical behaviours, echo- and paliphenomena; and Factor 4 (APF4) was course. Although the familial nature of Tourette syndrome and characterised by the absence of grunting tics and the presence of chronic tics has been well-documented,3 and twin studies impli- finger and hand tapping that was distinguished from finger and cate genetic and non-genetic factors in the expression of Tourette hand tics or forced touching. Robertson & Cavanna25 reported syndrome,4,5 specific, replicable findings for genetic loci have been the results of a principal components factor analysis completed somewhat elusive. To date, ten genetic linkage/association studies on 69 individuals with Tourette syndrome and chronic tics, all have been published.6–15 Regions of interest have been reported of whom were members of a large extended Tourette syndrome for chromosomes 2, 3, 4, 5, 8, 9, 10, 11, 13, 17 and 19. All of these pedigree.26 It should be noted that these investigators included findings are potentially very important, but none has yet been symptoms of other psychopathology (that are generally not con- replicated. Given strong evidence that Tourette syndrome is sidered to be tics, such as symptoms of inattention, hyperactivity, genetic and the lack of significant replicable linkage, combined obsessionality, compulsivity, depression and anxiety) in their with association findings showing that the underlying genetic principal components factor analysis. Three factors were observed: mechanisms are complex and likely to be heterogeneous, the Factor 1 (RCF1) consisted of predominantly ‘pure tics’ (both simple question arises as to whether there may be a way to disaggregate and complex motor and vocal/phonic tics); Factor 2 (RCF2) this heterogeneity to allow for clearer targets for clinical and included ‘ADHD and aggressive behaviours’, and complex motor genetic research. and vocal/phonic tics, including coprophenomena; and Factor 3 Investigators have employed a variety of methods that address (RCF3) was characterised by ‘depression–anxiety–obsessional multiple quantitative phenotypic dimensions, making it possible symptoms and self-injurious behaviour’ and compulsive-like tics, to examine distinct components of complex phenotypes. Studies including counting and ‘evening-up’. Finally, Mathews et al24 of reading disability,16 attention-deficit hyperactivity disorder reported results of hierarchical agglomerative cluster analysis (ADHD),17,18 obsessive–compulsive disorder (OCD)19 and aut- (HACA) from two genetically isolated populations (Costa Ricans ism20 have used various methods to discern possible underlying and Ashkenazi Jews) consisting of 254 individuals with Tourette phenotypic constructs. There have been few attempts to formally syndrome. These investigators observed two clusters which were classify people with Tourette syndrome on the basis of their tic essentially the same in the two genetic isolates: one characterised phenomenology.21,22 Robertson et al22 reported that coprolalia by simple motor and vocal/phonic tics and the other by com- and echophenomena were related to obsessional symptoms and plex motor and vocal/phonic tics. Thus, the results of all of these increased severity. To date, three cluster and/or factor analytic studies suggest that Tourette syndrome is not a unitary disorder investigations of tic phenomenology have been undertaken.23–25 and can be disaggregated into more homogeneous components. 31 Downloaded from https://www.cambridge.org/core. 24 Sep 2021 at 16:32:49, subject to the Cambridge Core terms of use. Robertson et al However, these studies had relatively small samples for principal HACA method progressively combines variables into related components analyses. Furthermore, one study included only clusters until all variables are subsumed into a single cluster, using related individuals25 and another24 examined genetically isolated the average linkage between-groups method to evaluate the populations. All of these call into question the generalisablity of Euclidean-squared cluster distances. The HACA does not rely on their results and speak to the need for a larger study of singleton preconceived characterisations concerning the number of clusters individuals with the syndrome. (such as specifying the number of clusters) or the relationships The primary aim of the current investigation was to identify between them (such as specifying the distances between clusters). quantitative components of Tourette syndrome symptomatology The stages of agglomeration are displayed as a dendrogram, with using a large, well-characterised sample of singleton individuals the formation of clusters at each stage plotted along a scaled stage with the syndrome. As noted by Verkerk et al,27 it is crucial in distance axis. For the current study, the best set of clusters future genetic studies of Tourette syndrome to search for more required to adequately represent the data was determined by homogeneous phenotypes of the syndrome. These investigators inspection of the dendrogram. There is no test of significance suggest that the use of factor-analysed quantitative symptom for clustering results other than their use in subsequent analyses. scores might prove useful. If such components can be identified For each resulting cluster, a score was then generated for each and can be examined in genetically informative data-sets, it could participant equal to the sum of the symptom variables contained lead to a major advance in future studies of Tourette syndrome. therein: symptom variables were scored 0 for never present and 1 for ever present. The resultant cluster scores were then used as input variables Methods for the principal components factor analysis. Principal compo- Participants nents factor analyses are typically based upon non-dichotomous variables; however, the variables that did not fall into a cluster The sample for this study consisted of 410 people with Tourette on the dendrogram were entered as dichotomous variables. The syndrome (75.9% male) who were seen at the National Hospital use of dichotomous variables can be justified in exploratory for Neurology and Neurosurgery (NHNN), Queen Square, approaches such as reported here. Using Kaiser–Guttman’s rule, London, UK. This research was approved by the ethics committee after factor extraction promax rotation was performed on factors at the NHNN for assessing both children and adults. Participants with eigenvalues greater than 1.0 (factors with eigenvalues less ranged in age from 3 to 59 years with a mean of 20.4 (s.d.=12.3). than 1.0 are generally spurious and non-reproducible) and All individuals over the age of 18 years gave informed consent. For compared. This procedure minimised the number of variables those individuals under the age of 18, parents gave informed with high loadings on each extracted factor and allowed for a consent for the children to be part of the study. All individuals more straightforward interpretation; other rotations were not were assessed and/or diagnosed with Tourette syndrome by the explored. Symptom loadings, with coefficient absolute values first author (M.M.R.) using
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