Neurological Soft Signs in

OCD Patients With Early

Age at Onset, Versus
Patients With Schizophrenia
and Healthy Subjects
Nematollah 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 schizophrenia and obsessive compulsive disorder (OCD) are
related to deviant neurodevelopment. Neurological
soft signs (NSS) have been proposed to be a marker
of abnormal brain development in schizophrenia.
The purpose of this study is to examine whether
NSS are also a marker in patients with OCD, in
particular, in early-onset OCD. The authors
included 162 subjects and compared patients with
OCD, patients with schizophrenia (SCZ), and
healthy control subjects. They were all examined for
NSS (Krebs Scale), extrapyramidal symptoms
(Simpson-Angus Scale), and were rated on the
Abnormal Involuntary Movements Scale (AIMS).
The authors found no differences between NSS total
scores and subscores in OCD versus controls,
whereas total NSS, motor coordination, and motor
integration were significantly lower in OCD than
in SCZ. OCD patients with early-onset (before age
13) did not differ from those with later-onset OCD.
These results support the idea that NSS, as determined by current scales, is relatively specific to
schizophrenia, although they do not preclude the

J Neuropsychiatry Clin Neurosci 23:4, Fall 2011

existence of a neurological dysfunction in OCD.

Further studies are required to determine the type
of neurological signs that could be useful traitmarkers in the phenotypic characterization of subtype OCD.
(The Journal of Neuropsychiatry and Clinical
Neurosciences 2011; 23:409 416)

bsessive-compulsive disorder (OCD), with a lifetime prevalence of 2.5% to 4%,1 is one of the most
prevalent and disabling psychiatric disorders. It is characterized by obsessions (which cause marked anxiety or
distress) 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 Clinical
Neurosciences Laboratory, Team Psychobiology of Compulsive Disorders; CIC INSERM U 802, Poitiers; Univ. Poitiers, CHU Poitiers;
Universite Paris Descartes, Laboratoire de Physiopathologie des Maladies Psychiatriques (LPMP), Centre DEvaluation et de Recherche
Clinique (CERC), Service Hospitalo-Universitaire de Sante Mentale et
Therapeutique, Centre Hospitalier Sainte-Anne, Paris; Department of
Psychiatry, Universite Rennes, France; Laboratoire Mouvement Adaptation Cognition, Universite Bordeaux, Bordeaux, France; Service
de Psychiatrie Adulte Hpitaux Universitaire Paris Sud, Assistance
Publique, des Hpitaux de Paris, 94278, Le Kremlin Bictre. Correspondence: Dr. Krebs; Marie-odile.krebs@inserm.fr; Dr. Jaafari,
n.jaafari@wanadoo.fr
Copyright 2011 American Psychiatric Association

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NEUROLOGICAL SOFT SIGNS, OCD, AND SCHIZOPHRENIA

ize anxiety). Neurological soft signs (NSS), in contrast
to hard neurological signs, are subtle neurological and
nonlocalizing anomalies, including altered motor coordination, balance, motor integration, and sensory integration. NSS may reflect cerebral dysfunction in distributed neural networks, and they can give additional
information on the functional organization that characterizes some psychiatric disorders.2 NSS have been described in several psychiatric disorders, but they are
particularly prevalent in schizophrenia.3 Only a few
studies have explored NSS in patients with OCD, and
their results are contradictory. There is only one previous study, by Bolton et al.,4 that compared NSS (assessed with the Cambridge Neurological Inventory) in
patients with OCD and patients with schizophrenia and
control subjects. In this study, as compared with patients with schizophrenia, patients with OCD had lower
levels of neurological signs, including motor coordination soft-signs, tardive dyskinesia, catatonic signs, and
extrapyramidal signs, and identical levels of NSS in
other subscales (sensory integration, primitive reflexes,
failure of suppression). This study has never been replicated. Other studies compared patients with schizophrenia 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 NSS
scores, restricted to sensory-integration items, as compared with controls. However, the same team, 2 years
later (Sevincok et al. [2006]6 and Poyurovsky et al.
[2007]7) did not find any significant differences in NSS
between patients with schizophrenia with or without
OCD. However, the number of OCD patients was low
in these studies (N 25). Finally, studies examining
NSS in patients with OCD, versus controls, also found
contradictory results. Some of these studies found a
higher prevalence of NSS in OCD patients than in
healthy controls,4,8 with impaired motor coordination
and visuospatial tasks,9 abnormal involuntary movements,9,10 sensory-integration abnormalities, and motor
overflow.11 However, other studies did not report such
differences,7,12,13 and, overall, the studies remain inconclusive because of intrinsic limitations; these observations were done in rather small samples,57 with no or
insufficient information on medication status or history,24,14 16 or extrapyramidal symptom assessment,8,12,13,17 and/or without a standardized examination.17,18 making any comparison difficult. It has been
suggested that NSS in OCD patients may be used as an

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early element of diagnosis4,19 or as predictors of good

treatment response to selective serotonin reuptake inhibitors20 or response to psychotherapy,21,22 but, here,
as well, there are contradictory findings.13,17,22,23 Overall, although some reviews state that NSS are increased
in OCD, a closer reading of previous studies reveals
that the picture is not very clear.
Like many psychiatric disorders, OCD is heterogeneous, and previous studies have stressed that children
with early onset (before age 7) are more likely to be
male and to have a family member with OCD than
those with later-onset OCD.24 Also, the age at onset is
earlier for boys (prepubertal onset) than for girls (during adolescence), with younger boys experiencing more
severe symptoms than younger girls.24 This suggests
that early age at onset of OCD reflects more neurodevelopmental loading than a later age at onset. In line
with this, early age at onset of OCD is more frequently
associated with tic disorders.2527
These investigations suggest that NSS may be higher
in patients with early age at onset of OCD than in
patients with later age at onset. However, to the best of
our knowledge, no study has directly examined the
influence of age at onset on NSS in patients with OCD.
Our primary objective in this study was to examine
NSS in patients with OCD as compared with patients
with schizophrenia and a control group. A secondary
objective was to look at whether OCD patients with an
early age at onset (before age 13) have more NSS than
other OCD patients or the control group, and less than
patients with schizophrenia.

METHOD
Participants
In this study, 162 subjects were recruited by three centers: the Centre Hospitalier Sainte-Anne, in Paris; the
Centre Hospitalier Henri Laborit, in Poitiers; and the
Centre Hospitalier Guillaume Regnier, in Rennes. This
protocol was approved by the ethics committee. All subjects received a complete description of the study and
gave written informed consent. All subjects with OCD
were consecutively-encountered patients of European
Caucasian descent who consented to participate to the
study. Patients with schizophrenia were selected in order
to match to OCD patients for gender and age, selected
from a large cohort of consecutively-encountered
European Caucasian patients with schizophrenia. This
study was part of a larger clinical and genetic research

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JAAFARI et al.
program and based on a national collaborative research
network (ReFaPsy).
These 162 subjects were divided into three groups:
patients with OCD (N54), patients with schizophrenia
(N54), and healthy control subjects (N54). Patients
were selected from both inpatient and outpatient clinical settings (33% and 66%, respectively). The percentage
of inpatients versus outpatients was 27% versus 33% for
patients with OCD and schizophrenia, respectively
(NS). The inpatients were included when stabilized, just
before discharge from the hospital. Controls were recruited from the administrative and paramedical staff
of the hospital and through advertisement, and received an incentive.
Patients and controls were examined with a standardized interview (DIGS: Diagnostic Interview Genetic Study) leading to lifetime diagnoses according
to DSM-IV criteria. For all subjects, exclusion criteria
were 1) current or history of neurological illness or severe
medical condition; 2) sequelae of trauma that could hinder
the neurological examination (e.g., wrist fracture); 3) recent (in the past year) substance abuse or dependence
and/or abuse or dependence lasting for more than 5
years; 4) clinically significant extrapyramidal symptoms
(Simpson-Angus Scale [SAS] 9 and Abnormal Involuntary Movement Scale [AIMS] 3).
Patients with OCD (18 53 years old) met the DSM-IV
criteria for OCD but not those for schizophrenia. Patients with schizophrenia (18 55 years old) met the
DSM-IV criteria for schizophrenia, but not those for
OCD. The control group comprised healthy volunteers
with no history of or current psychiatric illness; they
were matched to the OCD group for age, gender, and
education level.
Age at onset was further determined in OCD patients
as the first time that the presence of symptoms was
noticed by the individual and/or a family member.28
Early-onset OCD (EO-OCD) patients were defined as
having an age at onset under 13 (and, conversely, lateonset OCD [LO-OCD] patients were defined as having an
age at onset at or later than 13), in order to subgroup
prepubertal onset, as suggested by Geller et al.29 Moreover, this threshold is consistent with a SPECT study reporting significant differences in brain functional activity
between early- and late-onset OCD by use of this cutoff.30
Measures
All subjects were interviewed by senior psychiatrists
using the French version of the Diagnostic Interview for

J Neuropsychiatry Clin Neurosci 23:4, Fall 2011

Genetic Studies, leading to lifespan DSM-IV Axis I disorder.31 The severity of obsessive and compulsive
symptoms was measured by the French version of the
Yale-Brown Obsessive-Compulsive scale (Y-BOCS).32 A
minimum total Y-BOCS score 15 and 1-year duration of obsessive-compulsive symptoms were required.
Psychopathology in patients with schizophrenia was
assessed by the French version of the Positive and Negative Syndrome Scale (PANSS).33
NSS were assessed with a standardized neurological
examination previously described and validated by
Krebs et al.34 This examination includes a 23-item scale
for NSS as well as SAS for parkinsonism, AIMS for
dyskinesia, the Edinburgh, Scotland, Inventory for Lateralization, and the Mini-Mental State Exam (MMSE),
for general cognitive functioning. The scale ranges from
0 to 3. It assesses 5 factors: 1) motor coordination (finger
opposition, fist-edge-palm, alternate movements of foot
and 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, graphesthesia, rightleft recognition); 4) involuntary
movements (mirror movements, abnormal movement);
and 5) quality of lateralization (lateral preference, R/L
confusion). This scale has good interrater reliability.34

Data Analysis
In the OCD patient group, five patients had tics and had
higher AIMS scores (12.8 [SD]: 5.2) than the remaining
patients. Because this group of patients with OCD and
tics was small, and tics can confound neurological examination, we decided to exclude them from the analysis. Sociodemographic clinical variables were described and compared between the three groups with
one-way ANOVA or chi-squared tests for categorical
data. Correlation analyses of clinical variables with total
scores and subscores of NSS were conducted with the
Pearson correlation coefficient. Because of the wellknown influence of antipsychotic medication on extrapyramidal symptoms and because the groups differed regarding previous exposure to antipsychotic
medication, we decided to adjust NSS on SAS score in
our analysis. ANCOVAs were performed for total
scores and subscores of NSS, and to evaluate contrasts
between OCD patients versus controls and OCD
patients versus the schizophrenic group; Bonferronis
correction was applied.

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TABLE 1.

Characteristics of Patients and Control Subjects

Control
(N54)

Gender (M/F)
23/31
Age, years
29.6 (8.8)
Education level, years 13.7 (2.8)
Age at onset, years
Duration of illness,
years
Y-BOCS
Total
Obsessions
Compulsions
PANSS
Total
Positive
Negative
AIMS
0
SAS
0.83 (1.24)
Medication
Antidepressant
Antipsychotic

OCD
(N49)
22/27
29.9 (9.1)
13.1 (3.3)
17.7 (7.1)
12.5 (9.0)

SCZ
(N54)
23/31
29.9 (9.3)
12.7 (2.9)
25.1 (8.6)
4.8 (6.2)

OCD vs.
SCZ
NS
NS
NS
p0.001
p0.001

22.2 (7.1)
10.8 (4.1)
11.5 (3.8)
80.1 (18.7)
18.3 (7.3)
20.8 (7.6)
0.40 (0.96) 0.41 (0.96)
2.04 (1.98) 2.85 (3.23)
43 (88%)
13 (26%)

7 (13%)
36 (67%)

NS
p0.18
p0.001
p0.001

Values are mean (standard deviation) for demographic and clinical

variables. In the last column, p values are for the comparison between
the two patient groups.
Controls: healthy control subjects; SCZ: patients with schizophrenia; OCD: patients with obsessive-compulsive disorders; Y-BOCS:
Yale-Brown Obsessive-Compulsive Scale Compulsion. total scores
and subscores: Obsessions and Compulsions; PANSS: Positive and
Negative Syndrome Scale; AIMS: Abnormal Involuntary Movement
Scale; SAS: Simpson-Angus scale for extrapyramidal symptoms.

RESULTS
Clinical Description
In the OCD group, 88% of patients (N43) were currently on SSRI antidepressants, and 26% (N13) were
currently being treated with antipsychotics. Age at onset was significantly (p 0.001) earlier in the OCD
group than in the schizophrenic group. In the schizophrenic group, 25.9% (N14) had never received antipsychotic medication, and 7.4% (N4) had been off antipsychotic medication for at least 3 months. The remaining
66.7% (N36) were being treated with antipsychotics and
13% (N7) with antidepressants. There were no significant differences for the remaining descriptive variables
between the two patient groups (Table 1).
Compulsion Y-BOCS scores were inversely correlated with age at onset (r 0.31; p0.03); the higher
the Y-BOCS scores, the lower the age at onset. Thirteen
OCD patients (33%; 7 women, 6 men) had an early age
at onset (13 years) of their first symptoms (EO-OCD).
Neurological Examination of Patients With OCD
In the OCD patients, the NSS total score did not correlate either with the severity of the YBOCS total score or
with the obsession or compulsion subscores.
EO-OCD patients did not differ from LO-OCD

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groups on extrapyramidal symptoms: AIMS (EO-OCD:

0.42 [0.9]; LO-OCD: 0.41 [0.99]; NS) or on SimpsonAngus (EO-OCD: 2.70 [2.5]; LO-OCD: 1.83 [1.8]; NS).
No significant differences (F[1,46]0.03; NS) were observed between EO-OCD and LO-OCD groups in the
NSS 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 Integration factor, EO-OCD : 1.85 [1.63]; LO-OCD: 1.63
[1.66]).
When comparing OCD patients with and without
treatment with antipsychotic medication, no significant
differences were found in NSS, Simpson-Angus, or in
AIMS 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 Control
Subjects
The AIMS scores were comparable in patients with
OCD and patients with schizophrenia (Table 1), the two
groups being significantly different from controls (respectively, p0.024, p0.032). Extrapyramidal symptoms assessed by the Simpson-Angus scale were significantly different among the three groups (p 0.0001):
the scores were higher in patients with OCD than in
controls (p0.024), and the scores of OCD patients were
not significantly different from patients with schizophrenia (Table 1). Therefore, NSS analyses were adjusted on the Simpson-Angus score.
The total NSS score and the subscores were not significantly different between OCD patients and controls,
whereas significant differences were observed between
patients with OCD and those with schizophrenia for
total score, motor coordination, and motor integration.
No differences were seen among groups for sensory
integration, involuntary movement, and lateralization
factors (Table 2).

DISCUSSION
Both OCD and schizophrenia are thought to reflect
abnormal brain development, and NSSs have been
demonstrated to be a valid marker of abnormal neurodevelopment in patients with schizophrenia. The main
aim of this study was to examine whether NSS could
also be a valid marker of deviant neurodevelopment in

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TABLE 2.

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

TOTAL NSS
MOTC
MOTI
SENSI
ABM
LAT

Control
(N54)

OCD
(N49)

SCZ
(N54)

F[2,153]

ANOVA
p valuea

OCD/SCZ
p valueb

6.2 (0.71)
2.7 (0.4)
1.1 (0.24)
1.54 (0.24)
0.45 (0.11)
0.48 (0.14)

6.1 (0.72)
2.2 (0.41)
1.2 (0.24)
1.7 (0.24)
0.48 (0.12)
0.51 (0.14)

11.5 (0.7)
6.1 (0.4)
2.0 (0.24)
2.2 (0.23)
0.47 (0.11)
0.74 (0.14)

18.4
27.2
4.3
2.04
0.025
1.03

0.001
<0.001
0.016
0.13
NS
NS

0.001
0.001
0.036
NS
NS
NS

Adjusted mean (for Simpson-Angus score) and standard deviation (SD) are given for total neurological soft signs (NSS) scores (TOTAL NSS),
and subscores: MOTC (Motor Coordination Factor), MOTI (Motor Integrative Function), ABM (Involuntary Movements Factor), SENSI (Sensory
Integration Factor), LAT (Quality of Lateralization Factor).
a
The p value is for comparisons between the three groups.
b
Post-hoc p value is for comparisons between the OCD and SCZ groups after Bonferroni correction. Significant differences are in bold. None
of the comparisons between OCD and the control group were significant. Controls: healthy control subjects; SCZ: patients with schizophrenia;
OCD: patients with obsessive-compulsive disorders.

patients with OCD. We compared OCD patients with

carefully-matched patients with schizophrenia and controls and found higher NSS scores in patients with
schizophrenia than in those with OCD, which did not
differ from controls. Furthermore, we found no differences in the NSS total scores or subscores in patients
with early- versus late-onset OCD (age 13 versus
13). Taken together, our findings do not support the
idea that NSS indicate neurodevelopmental brain
anomalies associated with OCD and suggest that NSS
could be more specific to the neurodevelopmental
anomalies associated with schizophrenia.
Our work has several features. First, the sample size
was larger or similar to those of previous reports. Second, the inclusion criteria were very strictly defined,
and the populations were well-matched. The two patient groups were well contrasted by excluding OCD in
patients with schizophrenia (in contrast to others studies57) and, conversely, psychotic symptoms in patients
with OCD. These diagnoses were done on the basis of
lifespan structured interviews based on DSM-IV criteria, which were used in some,4 10,12,13 but not all2,18
previous reports. Possible confounding factors were
avoided by excluding, in particular, neurological disorders and substance abuse, information that is available
in some,4 7,12 but not all studies.13,17,22 We also carefully
matched 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 but
not all9,13,20,22 previous reports. Notably, this comprises
semiquantitative rather than presence/absence ratings
of NSS and could thus be more accurate, but could also
lead to some differences from previous studies.57,12
Fourth, the two groups of patients included patients

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naive for antipsychotic medication, including patients

with schizophrenia, which was not the case in previous
reports.4 6,9,12,17 Also, we took into account the extrapyramidal status of the patients. In contrast with previous reports,12,17 all subjects were examined not only
for NSS, but also for involuntary movements and
parkinsonism (using the well-validated AIMS35 and
SAS36 scales, respectively). Because differences were
observed between the two patient groups for parkinsonism, as measured by SAS, we adjusted the comparison SAS scores. We also made the decision to
exclude patients with tics, who may constitute a specific group with regard to neurological condition and
possibly underlying pathobiology. In previous studies, it is unclear whether patients with tics were included.4 9,12,13,17,20,22,37
Several limitations to this study should nevertheless
be discussed. First, the sample size remained relatively
small, despite being larger than in previous studies, and
we cannot exclude a lack of power to detect differences,
especially when subgrouping the patients with regard
to their age at onset. Also, we were not able to analyze
separately the patients with tics, although they appear
to have specific neurological features. Second, the later
age at onset and shorter duration of illness of patients
with schizophrenia could potentially bias the results in
favor of finding higher NSS scores in OCD patients.
Moreover, as would be expected, the groups were different with respect to psychotropic administration.
To assess the effects of medication on NSS, it was
impossible to introduce, in a linear-regression analysis,
either chlorpromazine-equivalents, because most of
OCD patients were not under antipsychotic medication,
or SSRI dose-equivalents, because most patients with

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NEUROLOGICAL SOFT SIGNS, OCD, AND SCHIZOPHRENIA

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 Movements
Factor; LAT: Quality of Lateralization factor.

schizophrenia did not take antidepressant medication,

and, of course, controls were not taking any medication.
However, the relationship between treatment effect and
psychotropic NSS remains controversial.8 Also, when we
compared patients with versus without antipsychotic and
with versus without antidepressant, we did not see any
significant differences. These are consistent with several
other studies that found no influence of medication on
NSS in OCD patients.5,17 or in patients with schizophrenia.14 16 Moreover, Hollander et al.8 report that NSSs
were more common in medication-free patients with
OCD than in controls. Last, the patients were not necessarily representative of all patients with OCD or schizophrenia. Although consecutively encountered, OCD patients were also selected for European Caucasian descent,
and patients with schizophrenia were additionally selected by age- and gender-matching with OCD patients.
Keeping in mind these limitations,4 6,10,17 we did
not replicate previous findings of an increase in NSS
in OCD patients as compared with controls and
rather found significantly lower NSS scores in those
patients than in patients with schizophrenia. Patients
with OCD had significantly lower total scores and
motor coordination subscores than patients with
schizophrenia (Figure 1). Our results are in line with
the Boltons study4 with a larger sample size that
compared OCD patients (N50) to patients with
schizophrenia and reported fewer NSS signs, less motor-coordination impairment, tardive dyskinesia, and
extrapyramidal signs (i.e., parkinsonism) in OCD,
including increased tone in limbs, decreased associated movements in walking, shuffling gait, arm-drop-

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ping, tremor, or neck rigidity in OCD patients than in

patients with schizophrenia. Also in line with their
observations, we did not observe any significant difference between the OCD group and the schizophrenia group in terms of sensory integration, involuntary movements, or quality of lateralization.
Our results suggest that the NSS we assessed in this
study are more severe in patients with schizophrenia
than in OCD patients; furthermore, we found no differences when comparing patients with OCD to healthy
controls. Our results are in line with two others studies
in which no differences in terms of NSS between patients with OCD and controls were found.12,13 However, two studies found neurological abnormalities in
patients 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 coordination
and visuospatial functions and also involuntary and
mirror movements. In the other one, Bolton et al.4
found that OCD patients had higher NSS scores than
the control group in motor coordination, sensory integration, and primitive reflexes, but also more extrapyramidal signs and deficient suppression. We did
not replicate those findings. Differences in medication status could partly explain these contradictory
findings. In Boltons study, 60% of patients (versus
26% in our study) were on medication,4 with no further details on the type of medication. Noteworthy,
although OCD patients had higher parkinsonism
scores than controls, comparisons of NSS were not
adjusted for this difference.4 In Hollanders study,
patients were medication-free for at least 2 weeks

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JAAFARI et al.
(with no further details on the mean duration of withdrawal and or the type of medication). This rather
short duration of withdrawal could be too limited to
avoid residual neurological side effects induced by
antidepressants and even more by antipsychotics.8
Several lines of evidence suggest that early age at
onset of OCD could be associated with more brain
anomalies.28 30 Nevertheless, to our knowledge, there
has been no other study examining the relationship
between NSS and age at onset in OCD. Two different
definitions of age at onset can be found in the literature:
1) the age at which symptoms were first noticed by the
individual and/or family member;28 2) the first time
that symptoms altered functioning.29 In this study, we
chose to use the former definition, since it is likely to
reflect the beginning of the disorder, whereas the latter
defines the onset of the syndrome and, as such, reflects
the severity of the symptoms.
We found no differences in NSS scores between EOOCD and LO-OCD groups or between EO-OCD and
healthy subjects, even when adjusting for age at time of
assessment (data not shown). Furthermore, no correlations were found between the severity of NSS and demographic variables such as educational level or severity of disease in the OCD group. These results are in line
with several other studies,6,12,37,38 although one study
has reported a positive correlation between the severity
of obsession and high levels of NSS.9 However, they did
not find any correlation between severity of disease
(Y-BOCS score total) and NSS.
Although NSS reflect dysconnectivity in distributed
networks, involving fronto-thalamo-cerebellar loops,39
the prevailing hypothesis regarding OCD suggests hyperactivity in the orbito-frontal cortex,29,40 medial caudate 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 with
schizophrenia from controls, appear to be relatively
specific to schizophrenia, whereas other neurological

subtle signs, not present in these scales, could be

worth exploring in OCD patients, in particular those
assessing the frontal-striatal loops. Further studies
are needed to explore neurological features of OCD in
more depth, using other neurological soft or hard
signs and extrapyramidal symptoms, and with a closer
look 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 Hospitalier Sainte Anne Hopital Sainte-Anne and by the Fondation
Pierre Deniker. The study was conceptualized by the principal investigator (MOK), and the funding source had no influence on the design or analysis of the study.
This study was promoted by Inserm and received financial
support from the Fondation Pierre Deniker. In Paris, the
study was conducted in the CERC, Centre d'Evaluation et de
Recherche Clinique with the help of Narjes Bendjemaa, Francoise Polides, Souhail Bannour, and Marie-Josee Dos Santos.
The study was supported by the Collaborative Network for
Family Study in Psychiatry (Reseau d'etude familiale en
Psychiatry, REFAPSY) and by the Fondation Pierre Deniker, and coordinated by Pr. M.O. Krebs, Hopital SainteAnne, Paris SHU: Pr. M.O. Krebs; SM 13,: Dr. M.N. Vacheron; SM 17,: Dr. F. Petitjean; SM 18: Dr. B. Garnier;
CMME, Paris; Pr. J. Guelfi; CH Les Mureaux; Dr. G. Naruse; C.H. Guillaume Regnier, Rennes; Pr. S. Tordjman, Pr.
B. Millet; C.H. Erasme Anthony; Dr. J.C. Pascal; C.H. Ville
Evrard, 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. Barthelemy; Fondation Lenval, Nice; Pr. F. Askenazy.
We also acknowledge Afsaneh Gray for the English editing
of the paper.
Authors Jaafari and Baup contributed equally to this work.

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