Jaafar in 2011

Neurological Soft Signs inOCD PatientsWith EarlyAge at Onset, VersusPatientsWith Schizophreniaand Healthy SubjectsNematollah Jaafari, M.D.Nicolas Baup, M.D., Ph.D.Marie-Chantal Bourdel, M.Sci.,Jean-Pierre Olie, M.D., Ph.D.Jean-Yves Rotge, M.D.Issa Wassouf, M.D.Igor Sharov, M.D.Bruno Millet, M.D., Ph.D.Marie-Odile Krebs, M.D., Ph.D.

Compelling evidence suggests that both schizophre-nia and obsessive compulsive disorder (OCD) arerelated to deviant neurodevelopment. Neurologicalsoft signs (NSS) have been proposed to be a markerof abnormal brain development in schizophrenia.The purpose of this study is to examine whetherNSS are also a marker in patients with OCD, inparticular, in early-onset OCD. The authorsincluded 162 subjects and compared patients withOCD, patients with schizophrenia (SCZ), andhealthy control subjects. They were all examined forNSS (Krebs Scale), extrapyramidal symptoms(Simpson-Angus Scale), and were rated on theAbnormal Involuntary Movements Scale (AIMS).The authors found no differences between NSS totalscores and subscores in OCD versus controls,whereas total NSS, motor coordination, and motorintegration were significantly lower in OCD thanin SCZ. OCD patients with early-onset (before age13) did not differ from those with later-onset OCD.These results support the idea that NSS, as deter-mined by current scales, is relatively specific toschizophrenia, although they do not preclude the

existence of a neurological dysfunction in OCD.Further studies are required to determine the typeof neurological signs that could be useful trait-markers in the phenotypic characterization of sub-type OCD.

(The Journal of Neuropsychiatry and ClinicalNeurosciences 2011; 23:409416)

Obsessive-compulsive disorder (OCD), with a life-time prevalence of 2.5% to 4%,1 is one of the mostprevalent and disabling psychiatric disorders. It is char-acterized by obsessions (which cause marked anxiety ordistress) and/or compulsions (which serve to neutral-

Received September 17, 2010; revised January 15, March 15, 2011;accepted March 31, 2011. From INSERM, Experimental and ClinicalNeurosciences Laboratory, Team Psychobiology of Compulsive Dis-orders; CIC INSERM U 802, Poitiers; Univ. Poitiers, CHU Poitiers;Universite Paris Descartes, Laboratoire de Physiopathologie des Mal-adies Psychiatriques (LPMP), Centre DEvaluation et de RechercheClinique (CERC), Service Hospitalo-Universitaire de Sante Mentale etTherapeutique, Centre Hospitalier Sainte-Anne, Paris; Department ofPsychiatry, Universite Rennes, France; Laboratoire Mouvement Ad-aptation Cognition, Universite Bordeaux, Bordeaux, France; Servicede Psychiatrie Adulte Hpitaux Universitaire Paris Sud, AssistancePublique, des Hpitaux de Paris, 94278, Le Kremlin Bictre. Corre-spondence: Dr. Krebs; [email protected]; Dr. Jaafari,[email protected]

Copyright 2011 American Psychiatric Association

J Neuropsychiatry Clin Neurosci 23:4, Fall 2011 http://neuro.psychiatryonline.org 409

ize anxiety). Neurological soft signs (NSS), in contrastto hard neurological signs, are subtle neurological andnonlocalizing anomalies, including altered motor coor-dination, balance, motor integration, and sensory inte-gration. NSS may reflect cerebral dysfunction in distrib-uted neural networks, and they can give additionalinformation on the functional organization that charac-terizes some psychiatric disorders.2 NSS have been de-scribed in several psychiatric disorders, but they areparticularly prevalent in schizophrenia.3 Only a fewstudies have explored NSS in patients with OCD, andtheir results are contradictory. There is only one previ-ous study, by Bolton et al.,4 that compared NSS (as-sessed with the Cambridge Neurological Inventory) inpatients with OCD and patients with schizophrenia andcontrol subjects. In this study, as compared with pa-tients with schizophrenia, patients with OCD had lowerlevels of neurological signs, including motor coordina-tion soft-signs, tardive dyskinesia, catatonic signs, andextrapyramidal signs, and identical levels of NSS inother subscales (sensory integration, primitive reflexes,failure of suppression). This study has never been rep-licated. Other studies compared patients with schizo-phrenia with or without OCD and healthy controls.57

Once again, the results are contradictory.Sevincok et al., in 2004,5 found that patients with

OCD-schizophrenia had significantly higher NSSscores, restricted to sensory-integration items, as com-pared with controls. However, the same team, 2 yearslater (Sevincok et al. [2006]6 and Poyurovsky et al.[2007]7) did not find any significant differences in NSSbetween patients with schizophrenia with or withoutOCD. However, the number of OCD patients was lowin these studies (N 25). Finally, studies examiningNSS in patients with OCD, versus controls, also foundcontradictory results. Some of these studies found ahigher prevalence of NSS in OCD patients than inhealthy controls,4,8 with impaired motor coordinationand visuospatial tasks,9 abnormal involuntary move-ments,9,10 sensory-integration abnormalities, and motoroverflow.11 However, other studies did not report suchdifferences,7,12,13 and, overall, the studies remain incon-clusive because of intrinsic limitations; these observa-tions were done in rather small samples,57 with no orinsufficient information on medication status or his-tory,24,1416 or extrapyramidal symptom assess-ment,8,12,13,17 and/or without a standardized examina-tion.17,18 making any comparison difficult. It has beensuggested that NSS in OCD patients may be used as an

early element of diagnosis4,19 or as predictors of goodtreatment response to selective serotonin reuptake in-hibitors20 or response to psychotherapy,21,22 but, here,as well, there are contradictory findings.13,17,22,23 Over-all, although some reviews state that NSS are increasedin OCD, a closer reading of previous studies revealsthat the picture is not very clear.

Like many psychiatric disorders, OCD is heteroge-neous, and previous studies have stressed that childrenwith early onset (before age 7) are more likely to bemale and to have a family member with OCD thanthose with later-onset OCD.24 Also, the age at onset isearlier for boys (prepubertal onset) than for girls (dur-ing adolescence), with younger boys experiencing moresevere symptoms than younger girls.24 This suggeststhat early age at onset of OCD reflects more neurode-velopmental loading than a later age at onset. In linewith this, early age at onset of OCD is more frequentlyassociated with tic disorders.2527

These investigations suggest that NSS may be higherin patients with early age at onset of OCD than inpatients with later age at onset. However, to the best ofour knowledge, no study has directly examined theinfluence of age at onset on NSS in patients with OCD.

Our primary objective in this study was to examineNSS in patients with OCD as compared with patientswith schizophrenia and a control group. A secondaryobjective was to look at whether OCD patients with anearly age at onset (before age 13) have more NSS thanother OCD patients or the control group, and less thanpatients with schizophrenia.

METHOD

ParticipantsIn this study, 162 subjects were recruited by three cen-ters: the Centre Hospitalier Sainte-Anne, in Paris; theCentre Hospitalier Henri Laborit, in Poitiers; and theCentre Hospitalier Guillaume Regnier, in Rennes. Thisprotocol was approved by the ethics committee. All sub-jects received a complete description of the study andgave written informed consent. All subjects with OCDwere consecutively-encountered patients of EuropeanCaucasian descent who consented to participate to thestudy. Patients with schizophrenia were selected in orderto match to OCD patients for gender and age, selectedfrom a large cohort of consecutively-encounteredEuropean Caucasian patients with schizophrenia. Thisstudy was part of a larger clinical and genetic research

NEUROLOGICAL SOFT SIGNS, OCD, AND SCHIZOPHRENIA

410 http://neuro.psychiatryonline.org J Neuropsychiatry Clin Neurosci 23:4, Fall 2011

program and based on a national collaborative researchnetwork (ReFaPsy).

These 162 subjects were divided into three groups:patients with OCD (N54), patients with schizophrenia(N54), and healthy control subjects (N54). Patientswere selected from both inpatient and outpatient clini-cal settings (33% and 66%, respectively). The percentageof inpatients versus outpatients was 27% versus 33% forpatients with OCD and schizophrenia, respectively(NS). The inpatients were included when stabilized, justbefore discharge from the hospital. Controls were re-cruited from the administrative and paramedical staffof the hospital and through advertisement, and re-ceived an incentive.

Patients and controls were examined with a stan-dardized interview (DIGS: Diagnostic Interview Ge-netic Study) leading to lifetime diagnoses accordingto DSM-IV criteria. For all subjects, exclusion criteriawere 1) current or history of neurological illness or severemedical condition; 2) sequelae of trauma that could hinderthe neurological examination (e.g., wrist fracture); 3) re-cent (in the past year) substance abuse or dependenceand/or abuse or dependence lasting for more than 5years; 4) clinically significant extrapyramidal symptoms(Simpson-Angus Scale [SAS] 9 and Abnormal Involun-tary Movement Scale [AIMS] 3).

Patients with OCD (1853 years old) met the DSM-IVcriteria for OCD but not those for schizophrenia. Pa-tients with schizophrenia (1855 years old) met theDSM-IV criteria for schizophrenia, but not those forOCD. The control group comprised healthy volunteerswith no history of or current psychiatric illness; theywere matched to the OCD group for age, gender, andeducation level.

Age at onset was further determined in OCD patientsas the first time that the presence of symptoms wasnoticed by the individual and/or a family member.28

Early-onset OCD (EO-OCD) patients were defined ashaving an age at onset under 13 (and, conversely, late-onset OCD [LO-OCD] patients were defined as having anage at onset at or later than 13), in order to subgroupprepubertal onset, as suggested by Geller et al.29 More-over, this threshold is consistent with a SPECT study re-porting significant differences in brain functional activitybetween early- and late-onset OCD by use of this cutoff.30

MeasuresAll subjects were interviewed by senior psychiatristsusing the French version of the Diagnostic Interview for

Genetic Studies, leading to lifespan DSM-IV Axis I dis-order.31 The severity of obsessive and compulsivesymptoms was measured by the French version of theYale-Brown Obsessive-Compulsive scale (Y-BOCS).32 Aminimum total Y-BOCS score 15 and 1-year dura-tion of obsessive-compulsive symptoms were required.Psychopathology in patients with schizophrenia wasassessed by the French version of the Positive and Neg-ative Syndrome Scale (PANSS).33

NSS were assessed with a standardized neurologicalexamination previously described and validated byKrebs et al.34 This examination includes a 23-item scalefor NSS as well as SAS for parkinsonism, AIMS fordyskinesia, the Edinburgh, Scotland, Inventory for Lat-eralization, and the Mini-Mental State Exam (MMSE),for general cognitive functioning. The scale ranges from0 to 3. It assesses 5 factors: 1) motor coordination (fingeropposition, fist-edge-palm, alternate movements of footand hand); 2) motor integrative function (Romberg test,finger to nose, gait, tandem walk, tongue protrusion,standing, walking heel-to-toe); 3) sensory integration(astereognosia, handface, constructive apraxia, gra-phesthesia, rightleft recognition); 4) involuntarymovements (mirror movements, abnormal movement);and 5) quality of lateralization (lateral preference, R/Lconfusion). This scale has good interrater reliability.34

Data AnalysisIn the OCD patient group, five patients had tics and hadhigher AIMS scores (12.8 [SD]: 5.2) than the remainingpatients. Because this group of patients with OCD andtics was small, and tics can confound neurological ex-amination, we decided to exclude them from the anal-ysis. Sociodemographic clinical variables were de-scribed and compared between the three groups withone-way ANOVA or chi-squared tests for categoricaldata. Correlation analyses of clinical variables with totalscores and subscores of NSS were conducted with thePearson correlation coefficient. Because of the well-known influence of antipsychotic medication on ex-trapyramidal symptoms and because the groups dif-fered regarding previous exposure to antipsychoticmedication, we decided to adjust NSS on SAS score inour analysis. ANCOVAs were performed for totalscores and subscores of NSS, and to evaluate contrastsbetween OCD patients versus controls and OCDpatients versus the schizophrenic group; Bonferroniscorrection was applied.

JAAFARI et al.


RESULTS

Clinical DescriptionIn the OCD group, 88% of patients (N43) were cur-rently on SSRI antidepressants, and 26% (N13) werecurrently being treated with antipsychotics. Age at on-set was significantly (p 0.001) earlier in the OCDgroup than in the schizophrenic group. In the schizo-phrenic group, 25.9% (N14) had never received antipsy-chotic medication, and 7.4% (N4) had been off antipsy-chotic medication for at least 3 months. The remaining66.7% (N36) were being treated with antipsychotics and13% (N7) with antidepressants. There were no signifi-cant differences for the remaining descriptive variablesbetween the two patient groups (Table 1).

Compulsion Y-BOCS scores were inversely corre-lated with age at onset (r 0.31; p0.03); the higherthe Y-BOCS scores, the lower the age at onset. ThirteenOCD patients (33%; 7 women, 6 men) had an early ageat onset (13 years) of their first symptoms (EO-OCD).

Neurological Examination of Patients With OCDIn the OCD patients, the NSS total score did not corre-late either with the severity of the YBOCS total score orwith the obsession or compulsion subscores.

EO-OCD patients did not differ from LO-OCD

groups on extrapyramidal symptoms: AIMS (EO-OCD:0.42 [0.9]; LO-OCD: 0.41 [0.99]; NS) or on Simpson-Angus (EO-OCD: 2.70 [2.5]; LO-OCD: 1.83 [1.8]; NS).No significant differences (F[1,46]0.03; NS) were ob-served between EO-OCD and LO-OCD groups in theNSS total score (EO-OCD: 5.9 [5.5]; LO-OCD: 6.2 [5.9])or subscores (Motor Coordination factor, EO-OCD: 1.85[1.99]; LO-OCD: 2.34 [3.15]; Motor Integrative function,EO-OCD: 1.38 [2.31]; LO-OCD: 1.09 [1.42]; Sensory In-tegration factor, EO-OCD : 1.85 [1.63]; LO-OCD: 1.63[1.66]).

When comparing OCD patients with and withouttreatment with antipsychotic medication, no significantdifferences were found in NSS, Simpson-Angus, or inAIMS scores. No significant differences (F[1,47]0.63;NS) were observed in NSS between EO-OCD (5.9 [5.5])and controls (5.38 [2.98]).

Comparisons in OCD, Schizophrenia, and ControlSubjectsThe AIMS scores were comparable in patients withOCD and patients with schizophrenia (Table 1), the twogroups being significantly different from controls (re-spectively, p0.024, p0.032). Extrapyramidal symp-toms assessed by the Simpson-Angus scale were signif-icantly different among the three groups (p 0.0001):the scores were higher in patients with OCD than incontrols (p0.024), and the scores of OCD patients werenot significantly different from patients with schizo-phrenia (Table 1). Therefore, NSS analyses were ad-justed on the Simpson-Angus score.

The total NSS score and the subscores were not sig-nificantly different between OCD patients and controls,whereas significant differences were observed betweenpatients with OCD and those with schizophrenia fortotal score, motor coordination, and motor integration.No differences were seen among groups for sensoryintegration, involuntary movement, and lateralizationfactors (Table 2).

DISCUSSION

Both OCD and schizophrenia are thought to reflectabnormal brain development, and NSSs have beendemonstrated to be a valid marker of abnormal neuro-development in patients with schizophrenia. The mainaim of this study was to examine whether NSS couldalso be a valid marker of deviant neurodevelopment in

TABLE 1. Characteristics of Patients and Control Subjects

Control(N54)

OCD(N49)

SCZ(N54)

OCD vs.SCZ

Gender (M/F) 23/31 22/27 23/31 NSAge, years 29.6 (8.8) 29.9 (9.1) 29.9 (9.3) NSEducation level, years 13.7 (2.8) 13.1 (3.3) 12.7 (2.9) NSAge at onset, years 17.7 (7.1) 25.1 (8.6) p0.001Duration of illness,

years12.5 (9.0) 4.8 (6.2) p0.001

Y-BOCSTotal 22.2 (7.1)Obsessions 10.8 (4.1)Compulsions 11.5 (3.8)

PANSSTotal 80.1 (18.7)Positive 18.3 (7.3)Negative 20.8 (7.6)

AIMS 0 0.40 (0.96) 0.41 (0.96) NSSAS 0.83 (1.24) 2.04 (1.98) 2.85 (3.23) p0.18Medication

Antidepressant 43 (88%) 7 (13%) p0.001Antipsychotic 13 (26%) 36 (67%) p0.001

Values are mean (standard deviation) for demographic and clinicalvariables. In the last column, p values are for the comparison betweenthe two patient groups.

Controls: healthy control subjects; SCZ: patients with schizophre-nia; OCD: patients with obsessive-compulsive disorders; Y-BOCS:Yale-Brown Obsessive-Compulsive Scale Compulsion. total scoresand subscores: Obsessions and Compulsions; PANSS: Positive andNegative Syndrome Scale; AIMS: Abnormal Involuntary MovementScale; SAS: Simpson-Angus scale for extrapyramidal symptoms.



patients with OCD. We compared OCD patients withcarefully-matched patients with schizophrenia and con-trols and found higher NSS scores in patients withschizophrenia than in those with OCD, which did notdiffer from controls. Furthermore, we found no differ-ences in the NSS total scores or subscores in patientswith early- versus late-onset OCD (age 13 versus13). Taken together, our findings do not support theidea that NSS indicate neurodevelopmental brainanomalies associated with OCD and suggest that NSScould be more specific to the neurodevelopmentalanomalies associated with schizophrenia.

Our work has several features. First, the sample sizewas larger or similar to those of previous reports. Sec-ond, the inclusion criteria were very strictly defined,and the populations were well-matched. The two pa-tient groups were well contrasted by excluding OCD inpatients with schizophrenia (in contrast to others stud-ies57) and, conversely, psychotic symptoms in patientswith OCD. These diagnoses were done on the basis oflifespan structured interviews based on DSM-IV crite-ria, which were used in some,410,12,13 but not all2,18

previous reports. Possible confounding factors wereavoided by excluding, in particular, neurological disor-ders and substance abuse, information that is availablein some,47,12 but not all studies.13,17,22 We also carefullymatched the three groups on age and gender. Third,patients were carefully tested, by use of a validated,standardized examination, in contrast to some,2,17,18 butnot all9,13,20,22 previous reports. Notably, this comprisessemiquantitative rather than presence/absence ratingsof NSS and could thus be more accurate, but could alsolead to some differences from previous studies.57,12

Fourth, the two groups of patients included patients

naive for antipsychotic medication, including patientswith schizophrenia, which was not the case in previousreports.46,9,12,17 Also, we took into account the extrapy-ramidal status of the patients. In contrast with previ-ous reports,12,17 all subjects were examined not onlyfor NSS, but also for involuntary movements andparkinsonism (using the well-validated AIMS35 andSAS36 scales, respectively). Because differences wereobserved between the two patient groups for parkin-sonism, as measured by SAS, we adjusted the com-parison SAS scores. We also made the decision toexclude patients with tics, who may constitute a spe-cific group with regard to neurological condition andpossibly underlying pathobiology. In previous stud-ies, it is unclear whether patients with tics were in-cluded.4 9,12,13,17,20,22,37

Several limitations to this study should neverthelessbe discussed. First, the sample size remained relativelysmall, despite being larger than in previous studies, andwe cannot exclude a lack of power to detect differences,especially when subgrouping the patients with regardto their age at onset. Also, we were not able to analyzeseparately the patients with tics, although they appearto have specific neurological features. Second, the laterage at onset and shorter duration of illness of patientswith schizophrenia could potentially bias the results infavor of finding higher NSS scores in OCD patients.Moreover, as would be expected, the groups were dif-ferent with respect to psychotropic administration.To assess the effects of medication on NSS, it wasimpossible to introduce, in a linear-regression analysis,either chlorpromazine-equivalents, because most ofOCD patients were not under antipsychotic medication,or SSRI dose-equivalents, because most patients with

TABLE 2. Covariance Analysis for NSS, With Simpson-Angus Score as Covariate

Control(N54)

OCD(N49)

SCZ(N54) F[2,153]

ANOVAp valuea

OCD/SCZp valueb

TOTAL NSS 6.2 (0.71) 6.1 (0.72) 11.5 (0.7) 18.4 0.001 0.001MOTC 2.7 (0.4) 2.2 (0.41) 6.1 (0.4) 27.2

schizophrenia did not take antidepressant medication,and, of course, controls were not taking any medication.However, the relationship between treatment effect andpsychotropic NSS remains controversial.8 Also, when wecompared patients with versus without antipsychotic andwith versus without antidepressant, we did not see anysignificant differences. These are consistent with severalother studies that found no influence of medication onNSS in OCD patients.5,17 or in patients with schizophre-nia.1416 Moreover, Hollander et al.8 report that NSSswere more common in medication-free patients withOCD than in controls. Last, the patients were not neces-sarily representative of all patients with OCD or schizo-phrenia. Although consecutively encountered, OCD pa-tients were also selected for European Caucasian descent,and patients with schizophrenia were additionally se-lected by age- and gender-matching with OCD patients.

Keeping in mind these limitations,4 6,10,17 we didnot replicate previous findings of an increase in NSSin OCD patients as compared with controls andrather found significantly lower NSS scores in thosepatients than in patients with schizophrenia. Patientswith OCD had significantly lower total scores andmotor coordination subscores than patients withschizophrenia (Figure 1). Our results are in line withthe Boltons study4 with a larger sample size thatcompared OCD patients (N50) to patients withschizophrenia and reported fewer NSS signs, less mo-tor-coordination impairment, tardive dyskinesia, andextrapyramidal signs (i.e., parkinsonism) in OCD,including increased tone in limbs, decreased associ-ated movements in walking, shuffling gait, arm-drop-

ping, tremor, or neck rigidity in OCD patients than inpatients with schizophrenia. Also in line with theirobservations, we did not observe any significant dif-ference between the OCD group and the schizophre-nia group in terms of sensory integration, involun-tary movements, or quality of lateralization.

Our results suggest that the NSS we assessed in thisstudy are more severe in patients with schizophreniathan in OCD patients; furthermore, we found no differ-ences when comparing patients with OCD to healthycontrols. Our results are in line with two others studiesin which no differences in terms of NSS between pa-tients with OCD and controls were found.12,13 How-ever, two studies found neurological abnormalities inpatients with OCD.4,8 In one of them, the authors8

found more NSS in OCD than in the control group,including impairments in fine motor coordinationand visuospatial functions and also involuntary andmirror movements. In the other one, Bolton et al.4

found that OCD patients had higher NSS scores thanthe control group in motor coordination, sensory in-tegration, and primitive reflexes, but also more ex-trapyramidal signs and deficient suppression. We didnot replicate those findings. Differences in medica-tion status could partly explain these contradictoryfindings. In Boltons study, 60% of patients (versus26% in our study) were on medication,4 with no fur-ther details on the type of medication. Noteworthy,although OCD patients had higher parkinsonismscores than controls, comparisons of NSS were notadjusted for this difference.4 In Hollanders study,patients were medication-free for at least 2 weeks

FIGURE 1. Means of NSS Sub-Scores in Patients With OCD, Those With Schizophrenia and Control Subjects

MOTC: Motor Coordination Factor; MOTI: Motor Integrative Function; SENSI: Sensory Integration Factor; ABM: Involuntary MovementsFactor; LAT: Quality of Lateralization factor.



(with no further details on the mean duration of with-drawal and or the type of medication). This rathershort duration of withdrawal could be too limited toavoid residual neurological side effects induced byantidepressants and even more by antipsychotics.8

Several lines of evidence suggest that early age atonset of OCD could be associated with more brainanomalies.2830 Nevertheless, to our knowledge, therehas been no other study examining the relationshipbetween NSS and age at onset in OCD. Two differentdefinitions of age at onset can be found in the literature:1) the age at which symptoms were first noticed by theindividual and/or family member;28 2) the first timethat symptoms altered functioning.29 In this study, wechose to use the former definition, since it is likely toreflect the beginning of the disorder, whereas the latterdefines the onset of the syndrome and, as such, reflectsthe severity of the symptoms.

We found no differences in NSS scores between EO-OCD and LO-OCD groups or between EO-OCD andhealthy subjects, even when adjusting for age at time ofassessment (data not shown). Furthermore, no correla-tions were found between the severity of NSS and de-mographic variables such as educational level or sever-ity of disease in the OCD group. These results are in linewith several other studies,6,12,37,38 although one studyhas reported a positive correlation between the severityof obsession and high levels of NSS.9 However, they didnot find any correlation between severity of disease(Y-BOCS score total) and NSS.

Although NSS reflect dysconnectivity in distributednetworks, involving fronto-thalamo-cerebellar loops,39

the prevailing hypothesis regarding OCD suggests hy-peractivity in the orbito-frontal cortex,29,40 medial cau-date nucleus, thalamus, and anterior cingulate gyrus,with no argument supporting dysconnectivity.

To conclude, NSS as assessed by the current scales,comprising items that discriminate patients withschizophrenia from controls, appear to be relativelyspecific to schizophrenia, whereas other neurological

subtle signs, not present in these scales, could beworth exploring in OCD patients, in particular thoseassessing the frontal-striatal loops. Further studiesare needed to explore neurological features of OCD inmore depth, using other neurological soft or hardsigns and extrapyramidal symptoms, and with a closerlook at the subgroup of OCD patients with tics.

All authors declare that they have no conflicts of interests.We thank all the patients and healthy volunteers involved.This work was supported by the Institut National de la

Sante et de la Recherche Medicale (Inserm), Centre Hospita-lier Sainte Anne Hopital Sainte-Anne and by the FondationPierre Deniker. The study was conceptualized by the princi-pal investigator (MOK), and the funding source had no in-fluence on the design or analysis of the study.

This study was promoted by Inserm and received financialsupport from the Fondation Pierre Deniker. In Paris, thestudy was conducted in the CERC, Centre d'Evaluation et deRecherche Clinique with the help of Narjes Bendjemaa, Fran-coise Polides, Souhail Bannour, and Marie-Josee Dos Santos.

The study was supported by the Collaborative Network forFamily Study in Psychiatry (Reseau d'etude familiale enPsychiatry, REFAPSY) and by the Fondation Pierre Deni-ker, and coordinated by Pr. M.O. Krebs, Hopital Sainte-Anne, Paris SHU: Pr. M.O. Krebs; SM 13,: Dr. M.N. Vach-eron; SM 17,: Dr. F. Petitjean; SM 18: Dr. B. Garnier;CMME, Paris; Pr. J. Guelfi; CH Les Mureaux; Dr. G. Na-ruse; C.H. Guillaume Regnier, Rennes; Pr. S. Tordjman, Pr.B. Millet; C.H. Erasme Anthony; Dr. J.C. Pascal; C.H. VilleEvrard, Saint-Denis; Dr. D. Januel, Dr. L. Stamatiadis;C.H.U. Strasbourg; Pr. J.M. Danion; Hopital Sud, Grenoble;Pr. T. Bougerol, Dr. M. Polosan; Hopital Laborit, Poitiers;Pr. J.L. Senon, Dr. N. Jaafari, M.E. C. Turque; C.H.U.Bretonneau, Tours; Dr. F. Bonnet-Brilhault; Pr. C. Barthe-lemy; Fondation Lenval, Nice; Pr. F. Askenazy.

We also acknowledge Afsaneh Gray for the English editingof the paper.

Authors Jaafari and Baup contributed equally to this work.

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