An Epidemiologic Study of Gilles de la Tourette's Syndrome in Israel

An Epidemiologic Study of Gilles de la Tourette'sSyndrome in IsraelAlan Apter, MD; David L. Pauls, PhD; Avi Bleich, MD; Ada H. Zohar, PhD; Shmuel Kron, MD; Gidi Ratzoni, MD;Anat Dycian, MA; Moshe Kotler, MD; Avi Weizman, MD; Natan Gadot, MD; Donald J. Cohen, MD

Objectives: The goal of this study was to estimate thelifetime prevalence of Gilles de la Tourette's syndrome(GTS) in adolescents aged 16 to 17 years.

Design: Population-based epidemiologic study.

Subjects: Eighteen thousand three hundred sixty-fourmales and 9673 females aged 16 to 17 years screened forinduction into the Israel Defense Force.

Results: Of the 28 037 individuals screened, 12 met diag-nostic criteria for GTS. The point prevalence in this popu-lation was 4.3\m=+-\1.2(mean\m=+-\SE)per 10 000. The 95% con-

fidence interval for this estimate is 1.9 to 6.7 per 10 000. Thepoint prevalencewas 4.9 \m=+-\1.6 per 10 000 for males (95% con-

fidence interval, 1.8 per 10 000) and 3.1 \m=+-\1.8per 10 000 for

females (95% confidence interval, 0 to 6.6 per 10 000). Therate ofobsessive-compulsive disorder (OCD) was significantlyelevated among the subjects with GTS (41.7%) comparedwiththe population point prevalence ofOCD (3.4) in those with-out GTS. In contrast, the rate ofattention deficit hyperactivitydisorder was only 8.3% comparedwith the population pointprevalence of 3.9% in those individuals without GTS.

Conclusions: The prevalence estimates from this pop-ulation-based study are in agreement with previous re-

sults based on surveys of younger children. The sex ratioobserved in this study is not as large as reported in Pre-vious studies and remains to be explored in other studiesof adolescents and adults.

(Arch Gen Psychiatry. 1993;50:734-738)

Gilles DE LA Tourette's syn¬drome (GTS) is a neu¬

ropsychiatrie disorderwith onset in childhood,characterized by motor

and phonic tics that wax and wane over

the course of the illness. During the pastdecade, GTS has been the focus of con¬siderable research1·2; however, few epide¬miologie studies have been conducted toestablish the prevalence of GTS in the gen¬eral population. In an early study, Lucasand colleagues3 searched for all cases ofGTSin a computerized diagnostic index main¬tained at the Mayo Clinic, Rochester, Minn.Twenty-seven patients were identified fromthis registry; however, not all came fromthe immediate Rochester area. To obtain a

better prevalence estimate, Lucas and col¬leagues attempted to ascertain all cases iden¬tified between 1968 and 1979 in Roches¬ter. Three individuals were located, yieldinga rate for this community of 0.046 per10 000.

A more recent study surveyed all phy¬sicians in the state of North Dakota in an

attempt to identify all patients with GTSin their care.4 The prevalence estimate forthis study was considerably higher than thatreported by Lucas and coworkers.3 Foradults, the total overall rate was 0.50 per10 000. The prevalence was estimated tobe 0.77 per 10 000 for males and 0.22 per10 000 for females. Among school-age chil¬dren, the total rate was estimated to be 5.2per 10 000, with a prevalence of 9.3 per10 000 for males and a prevalence of 1.0per 10 000 for females.

A shortcoming of both of these stud¬ies was the reliance on identified treatedcases. To address this problem, a study of

From the Geha PsychiatricHospital, Department of Childand Adolescent Psychiatry,Sackler School of Medicine, TelAviv University, Petah Tikva,Israel (Drs Apter, Ratzoni,Weizman, and Gadot); theDepartment of Psychiatry,Sakler School of Medicine, TelAviv University, Ramat Aviv,Israel (Drs Apter, Bleich, andRatzoni); Israel Defense Force(Drs Apter, Bleich, Kron, andRatzoni and Ms Dycian); theChild Study Center (Drs Pauls,Zohar, and Cohen) and theDepartment of Genetics(Dr Pauls), Yale UniversitySchool of Medicine, New Haven,Conn; the Department ofPsychology, Hebrew University,Jerusalem, Israel (Dr Zohar);and the Department ofPsychiatry, Albert EinsteinCollege of Medicine, New York,NY (Dr Kotler).

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SUBJECTS AND METHODS

SAMPLE

The sample consisted of a cohort of 16- to 17-year-old Is¬raelis screened at an Israel Defense Force induction centerin Israel. Some institutionalized individuals (0.02%) werenot personally evaluated, but extensive information aboutthem was available from medical records. All medical recordsfrom institutionalized adolescents were evaluated by threeboard-certified child psychiatrists (A.A., G.R., and A.W.) todetermine whether any of them met criteria for GTS; noindividuals with GTS were identified. Females who claimedexemption from the military on religious grounds (on av¬

erage, 5% of the general Israeli population) were not in¬cluded in the study.

All subjects were screened for lifetime occurrence ofmotor and/or phonic tics at the time of preliminary induc¬tion evaluations. Altogether, more than 28 000 individualswere assessed during a 1-year period.ASSESSMENT PROCEDURE

A three-stage ascertainment procedure was used to identifyaffected individuals. The initial screening stage utilized a four-item self-report questionnaire (Table I ) that elicited infor¬mation about the lifetime occurrence of tics. After comple¬tion of the questionnaire, each subject was examined by aninduction center physician who was trained to recognize ticsand GTS. Altogether, 12 psychiatrists participated in the first-stage screening. All of them were trained by a board-certifiedchild psychiatrist experienced with GTS (A.W.). The train¬ing included lectures and audio-visual materials obtained fromthe GTS clinic at the YaleUniversity Child Study Center, NewHaven, Conn. All 12 Israel Defense Force clinicians specif¬ically asked the same four questions, reviewed the writtenresponses, and observed the young people to assess the pres¬ence of tics. For quality assurance, each physician signed thequestionnaire after the physical examination. All individualswho responded positively to at least one screening questionwere included in the second stage of the evaluation.

In the second stage of ascertainment, all individualswere examined clinically by one of three board-certified childpsychiatrists (A.A., G.R., and A.W.) with special researchinterest and training for the diagnosis of tic disorders. Thesecond stage of the assessment consisted of a nonstructuredclinical interview that assessed general psychopathology anddetermined the nature of tics, if present, and the course ofthe tic disorder. If, after this interview, the clinician be¬lieved that the individual possibly met DSM-III-R criteriafor GTS, the adolescent was included in the third stage ofthe ascertainment process.

In the third stage, individuals were formally adminis¬tered the Yale Schedule for Tourette's Syndrome and OtherBehavioral Syndromes (YSTSOBS)7 by a member of the sameteam of child psychiatrists that conducted the second-stageinterviews. The YSTSOBS is a precoded structured inter¬view developed specifically for a family study of GTS.8 Thetic section of this interview grew out of a questionnaire firstdeveloped for a survey designed to collect information aboutthe presence and severity of tic symptoms from the mem¬

bership of the Tourette Syndrome Association.9 The mostinformative and reliable items from that questionnairewere combined with items from rating scales developedfor clinical assessment of GTS and related disorders.10The OCD section of the interview was developed fromitems included in the Yale-Brown Obsessive CompulsiveScale.11 Specifically, items that elicit information regard¬ing the presence of obsessions and compulsions, thesenselessness or repugnance of those symptoms, andresistance to the thoughts and behaviors are included.Furthermore, the YSTSOBS includes the Schedule for Af¬fective Disorders and Schizophrenia for School-age Chil¬dren,12 which enabled assessment of any psychiatric dis¬order during the adolescent's lifetime.

To determine the sensitivity and specificity of the four-item screening instrument, 562 consecutive individuals whocompleted the four-item screening instrument were inter¬viewed by trained child psychiatrists (G.R. and A.A.) whowere "blind" to the responses on the screening question¬naire. The interviewers completed the sections of theYSTSOBS that elicited information necessary for diagnosesof GTS and tics, OCD, and ADHD.

school-age children was conducted in Monroe County,New York.3 In this study, individuals were identified throughreferrals resulting from public announcements, contact withthe public and private schools, and mailings to physi¬cians and other treating health care professionals. Chil¬dren who were identified through this screening were thor¬oughly evaluated by the team of researchers using a batteryof standard instruments. With use of this two-stage as¬

certainment scheme, the population prevalence was es¬

timated to be 2.9 per 10 000.In the most recent study,6 selected classrooms in a

southern California school district were surveyed. Achild study team that consisted of a psychologist, a

nurse, a speech and language specialist, a principal,and teachers received student referrals from teachersand parents for psychoeducational assessments. Duringthese interactions with the children, the school psy¬chologist observed children for motor and vocal tics.Children were referred from among more than 3000students in three schools during a period of 2 years.The sample included an overrepresentation of full-dayspecial education classes. Prevalence rates were esti¬mated correcting for the number of special classes andincluding individuals who met criteria for GTS, exceptthat the symptoms had not been present for 1 year.The frequency of GTS was reported to be 105.3 per



10 000 for males and 13.2 per 10 000 for females.While the Monroe County5 and southern California6studies obtained cases from sources other than physi¬cians, neither conducted a general population screen¬

ing for tics. Thus, to our knowledge, no study has sys¬tematically screened all individuals in a population fortics who were then followed up with a systematic clin¬ical evaluation for the presence of GTS.

Israel provides a unique opportunity for population-based studies of developmental psychopathology in ad¬olescence. Between the ages of 16 and 17 years, allJewish and Druze adolescents are evaluated for physi¬cal, psychological, and cognitive fitness in preparationfor army service. The only exceptions are some reli¬gious girls. Furthermore, because individuals can beobserved closely throughout their military service andbecause males who serve in the reserves can be fol¬lowed up for many years, there is an opportunity tolearn more about the course of the disorder identifiedin a population survey.

We took advantage of this complete population screen¬ing in Israel. Approximately 28 000 adolescents betweenthe ages of 16 and 17 years who were being screened formilitary induction were also screened for the presence oftics. Our goals were to estimate (1) the point prevalenceofGTS, (2) the role of obsessive-compulsive disorder (OCD),and (3) attention-deficit hyperactivity disorder (ADHD)among the individuals with GTS identified from a largeunselected population-based sample.

The cohort of individuals with GTS identified in thisinitial screening are being followed through the course oftheir military experience to determine the effect of stresson the manifestation of the disorder. Gilles de la Tourette'ssyndrome is a well-defined neuropsychiatrie entity withimportant implications for the study of child and ado¬lescent development and lends itself to a developmentalepidemiologie approach. Such a study of GTS could pro¬vide a model for the study of similar psychopathologicconditions as they develop through adolescence intoadulthood.

RESULTS

A total of 18 364 males and 9673 females between theages of 16 and 17 years were screened. The disparity inthe number of males and females reflects the fact that thisinduction center specializes in the induction of males. Thus,there are normally more males than females seen for screen¬ing at this location. The only selection criterion is gender;thus, the prevalence estimates should not be affected ex¬

cept that the estimate for females will have a larger SE.Nine males and three females were diagnosed as hav¬

ing GTS. The point prevalence was 4.9±1.6 (mean±SE)per 10000 for males and 3.1±1.8 per 10000 for fe¬males. The 95% confidence intervals were 1.8 to 8.0 and0 to 6.6 per 10 000 for males and females, respectively.The overall point prevalence in this sample was 4.3 ± 1.2per 10 000 (95% confidence interval, 1.9 to 6.7 per 10 000).The male-to-female ratio was approximately 1.6:1.

The disorders associated with GTS are shown inTable 2. Five (41.7%) of the 12 individuals had OCD;only one (8.3%) had ADHD. The individual with ADHDalso had OCD and a wide range of other behavioralproblems.

Of the 562 individuals included in the sensitivity study,11 were diagnosed as having a tic disorder. Of these 11individuals, one met criteria for GTS and 10 had chronictics. Only one of these 11 denied having tics during theinitial screening. Thus, the sensitivity of the initial screen¬ing instrument to identify tics was excellent (0.91); how¬ever, the specificity was quite low. Of the 562 individualsin this substudy, 62 answered positively to one of theitems on the screening instrument. As indicated above,only 10 of those 62 actually met criteria for either chronictics or GTS. An additional four individuals met criteriafor transient tic disorder. While the specificity of this screen¬ing method is low, for the purposes of our study, it wascritical to have the sensitivity of the screening instrumentas high as possible so as not to miss any affected indi¬viduals. No individual who denied having tics on the screen¬ing questionnaire was determined to have GTS.

As indicated above, all 562 individuals were inter¬viewed to assess the lifetime occurrence ofOCD and ADHD.As seen in Table 1, the initial screening questionnaire didnot include any questions regarding obsessions and com¬pulsions or symptoms of inattention, impulsivity, or hy¬peractivity. It was important to obtain an estimate of theprevalence of OCD and ADHD in this sample to betterevaluate the rates of these two conditions among the in¬dividuals with GTS. While our sample is quite small, itcan be used to determine the point prevalence of OCDand ADHD in a random sample of 16- to 17-year-old in¬dividuals in which all individuals were personally inter¬viewed. Of the 562 inductees interviewed, 19 were di¬agnosed as having OCD (3.4%), four (21.0%) of whomhad had tics at some point in their lives. A total of 22



*OCD indicates obsessive-compulsive disorder; ADD, attention-deficit disorder; ADHD, attention-deficit hyperactivity disorder; minus sign, not present; andplus sign, present.

individuals were determined to have a lifetime diagnosisof ADHD (3.9%). Only one (4.5%) of these 22 had hadchronic tics.

COMMENT

To our knowledge, ours is the first population-based studythat has systematically screened a large unselected sam¬

ple for the presence of GTS. The overall prevalence esti¬mate (4.2 per 10 000) we obtained is consistent with priorestimates.4·5 This is somewhat surprising, because all pre¬vious studies relied in some part on cases seen by a phy¬sician or some other health care professional. In addition,the sex ratio obtained was somewhat lower than that re¬ported in previous studies. As noted, the prevalence wasestimated at 4.9 per 10 000 for males and 3.1 per 10 000for females, resulting in a male-to-female ratio of 1.6:1.This is different from the previous findings in which maleswere at least three to four times more likely than femalesto have GTS.

It is not immediately clear why the prevalence andthe sex ratio are so low. In all previous studies, individ¬uals with GTS were identified through either health care

professionals or referral from special agencies. If there issome referral bias, such that males are more likely thanfemales to be taken for help or put into special educationclasses, then the ratio observed in these earlier studieswould be too large.

On the other hand, it is possible that the prevalenceestimates in our study are too low. Given the desirabilityof being in the army in Israel, it is possible that theseindividuals denied the existence of tics. However, the na-

ture of the induction process and the scrutiny of the eval¬uation make it unlikely that an individual would be ableto suppress tics for the entire time of the assessment. Thus,it is doubtful that denial is an important factor. Further¬more, the results of the sensitivity study suggest that ourscreening process was excellent for identification of sub¬jects with GTS. However, it is still possible that a sub¬stantial number of subjects denied ever having tics whenin fact that was not true. Because it was not possible toobtain information from other sources (ie, family mem¬

bers, teachers, or peers), it was impossible to determinewith independent data whether tics did occur at someearlier time.

Our findings are consistent with the hypothesis thatOCD is part of the clinical presentation of GTS in thatapproximately 40% of all individuals with GTS were alsodiagnosed as having OCD. Given that this is a sample of16- to 17-year-old adolescents, this is probably an un¬

derestimate of the true frequency of OCD among patientswith GTS. It would be expected that some of these indi¬viduals will eventually develop OCD.

In contrast, our findings do not support the hy¬pothesis that ADHD is part of the clinical presentationof GTS.13 Only one (8.3%) of the 12 subjects with GTSwas also diagnosed as having ADHD. This rate is notsignificantly different from the rate obtained in thispopulation (3.9%). However, while these findings sup¬port the hypothesis that the high rate of ADHD seen inclinical samples of patients with GTS may result fromascertainment bias similar to that described by Berk-son14 and Pauls et al,15 a caveat must be noted. It isvery difficult to assess ADHD reliably. This is particu-



larly true if the assessment is done in a retrospectivefashion, as was the case in our study. Furthermore, ad¬olescents are not likely to be highly reliable reportersof symptoms associated with ADHD. Unfortunately, noother data were available regarding ADHD symptoms.As discussed above, it was not possible to interviewparents, nor was it possible to obtain school or medicalrecords regarding childhood behavioral difficulties.Thus, these findings must be interpreted with caution.A much better research design to determine the rela¬tionship between GTS and ADHD would include a

prospective longitudinal study of children at risk forboth disorders. It will only be possible to fully under¬stand the relationship between the two conditions withcareful direct evaluation of children at risk with theuse of a variety of strategies designed to fully assess thecomplete symptom profile of both disorders.

Although we screened a large sample of individu¬als, the identified cohort of subjects with GTS is stilltoo small. Larger samples are needed so that analysesthat examine onset, severity, and course of illness can

be conducted for a non-clinic-based sample. Previouswork has suggested that only a minority of individualswith GTS actually seek help for their disorder.5 Thus,it is important to identify cases from additional epide¬miologie studies so that it will be possible to under¬stand more completely the full range of expression andnatural course of GTS.

Accepted for publication June 26, 1992.This work was supported in part by grantsfrom the Tourette

Syndrome Association (Dr Apter, principal investigator), theNational Institutes of Health, Bethesda, Md (grant NS-16648, Dr Pauls, principal investigator), and the NationalInstitute of Mental Health, Rockville, Md (grant MH-00508,a Research Scientist Development Award to Dr Pauls).

The authors express appreciation to ProfY. Danon, formerchief of the Israel Defense Force Medical Corps, the physi¬cians at the induction center where the sample was collected,and Anat Hoffman for her contribution to the success of thiswork. Finally, the authors express appreciation to two anon-

ymous reviewers for comments that substantially improvedthe manuscript.

Reprint requests to the Child Study Center, Yale Uni¬versity School of Medicine, 230 S Frontage Rd, New Haven,CT 05610 (Dr Pauls).

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Health & Medicine

An Epidemiologic Study of Gilles de la Tourette's Syndrome in Israel